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NCI CANCERLIT^® Search: Endometrial Cancer - September 2002

National Cancer Institute^®
Last Modified: September 1, 2002

Can radiological procedures replace histologic examination in the evaluation of abnormal vaginal bleeding?
Endometrial thickness as a test for endometrial cancer in women with postmenopausal vaginal bleeding.
Endometrial mixed Mullerian tumor with heterologous elements following tamoxifen therapy for breast cancer: a case report and literature
Expression of cyclin A in endometrial adenocarcinoma and its correlation with proliferative activity and clinicopathological variables.
Incidence of cardiovascular disease, cancer and death in postmenopausal women affirming use of hormone replacement therapy.
Advances in the management of endometrial adenocarcinoma. A review.
Up-regulation of cyclooxygenase-2 expression and prostaglandin synthesis in endometrial stromal cells by malignant endometrial epithelial cells.
Cigarette smoking and the risk of endometrial cancer.
Cervical cytology and immunohistochemical features in endometrial adenocarcinoma simulating microglandular hyperplasia. A case report.
A binary architectural grading system for uterine endometrial endometrioid carcinoma has superior reproducibility compared with FIGO
Molecular pathology of endometrial hyperplasia and carcinoma.
Aggressive endometrial carcinoma in a breast cancer patient treated with tamoxifen with normal transvaginal ultrasonography. Case report.
Comparison of two procedures for sentinel lymph node detection in patients with endometrial cancer: a pilot study.
Evaluation of morbidity after external radiotherapy and intracavitary brachytherapy in 771 patients with carcinoma of the uterine cervix or
Immunohistochemical investigation of p-53, C-NEU and EGFR expression in HPV-related epidermoid endometrial carcinoma.
Cavernous hemangioma of the uterus (a case report).
Endometrial cancer.
Lymphadenectomy and adjuvant therapy in endometrial carcinoma: role of adjuvant chemotherapy.
[Latest information of therapeutic approach for endometrial cancer]
Inguinal lymph node metastasis as the presenting symptom of endometrial cancer: a case report.
Association of hypoxia-inducible factors 1alpha and 2alpha with activated angiogenic pathways and prognosis in patients with endometrial
Regulation of keratinocyte growth factor expression in human endometrium: implications for hormonal carcinogenesis.
Frameshift mutations at mononucleotide repeats in caspase-5 and other target genes in endometrial and gastrointestinal cancer of the
Analysis of the candidate target genes for mutation in microsatellite instability-positive cancers of the colorectum, stomach, and
Screening families with endometrial and colorectal cancers for germline mutations.
Stage I-II endometrial adenocarcinoma evolution of therapeutic paradigms: the role of surgery and adjuvant radiation.
Early detection of endometrial cancer by combined use of vaginal ultrasound and endometrial vacuum sampling.
Immunohistochemical evaluation is not prognostic for recurrence in fully staged high-risk endometrial cancer.
Cervical implant from villoglandular endometrial adenocarcinoma masquerading as cervical villoglandular adenocarcinoma.
Prognostic significance of Bcl-2, p53 overexpression, and lymph node metastasis in surgically staged endometrial carcinoma.
Endometrial safety of hormone replacement therapy: review of literature.
Urokinase plasminogen activator receptor: Prognostic biomarker for endometrial cancer.
Cyclooxygenase-2 expression in endometrial carcinoma: correlation with clinicopathologic parameters and clinical outcome.
Genetic progression in sporadic endometrial and gastrointestinal cancers with high microsatellite instability.
PTEN expression is associated with prognosis for patients with advanced endometrial carcinoma undergoing postoperative chemotherapy.
Is the telomerase assay useful for screening of endometrial lesions?
hCDC4 gene mutations in endometrial cancer.
Significant increase of benign endometrial cells on Papanicolaou smears in women using hormone replacement therapy.
Angiogenesis and Bcl-2 protein expression in patients with endometrial carcinoma.
TP53 protein expression analysis by luminometric immunoassay in comparison with gene mutation status and prognostic factors in early
Tissue and serum CA125 expression in endometrial cancer.
Endometrioid carcinoma of the endometrium with an invasive component of minimal deviation carcinoma.
Endometrial stromal sarcomas with unusual histologic features: a report of 24 primary and metastatic tumors emphasizing fibroblastic and smooth
TSG101 expression in gynecological tumors: relationship to cyclin D1, cyclin E, p53 and p16 proteins.
Long-term outcome in endometrial carcinoma favors a two- instead of a three-tiered grading system.
Adjuvant chemotherapy in stage I uterine endometrial carcinoma.
Is there a survival benefit to adjuvant radiotherapy in high-risk surgical stage I endometrial cancer?
Bax, Bcl-2, and p53 expression in endometrial cancer.
Shortcomings and deficits in surgical treatment of gynecological cancers: a German problem only?
Chylous ascites following treatment for gynecologic malignancies.

1
UI - 12039104
AU - Runowicz CD
TI - Can radiological procedures replace histologic examination in the evaluation of abnormal vaginal bleeding?
SO - Obstet Gynecol 2002 Apr;99(4):529-30

2
UI - 12039131
AU - Tabor A; Watt HC; Wald NJ
TI - Endometrial thickness as a test for endometrial cancer in women with postmenopausal vaginal bleeding.
SO - Obstet Gynecol 2002 Apr;99(4):663-70
AD - Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Hvidovre, Denmark. ann.tabor@hh.hosp.dk
OBJECTIVE: To assess the value of endometrial thickness measurement as a test for endometrial cancer in postmenopausal women with vaginal bleeding (symptomatic women). DATA SOURCES: We conducted a literature search using the MEDLINE database from 1991 to 1997, and the key words "vaginal ultrasonography" and "endometrial thickness measurement." The review was limited to original research reports written in English, concerning symptomatic women having vaginal ultrasonography before a diagnostic test and not receiving tamoxifen. STUDY SELECTION: A total of 48 studies were identified. A questionnaire was sent to the corresponding author of each paper requesting supplementary information. Data were included in our analysis if the corresponding author was able to supply information on the median endometrial thickness in unaffected symptomatic women and the endometrial thickness values in affected women. Nine studies were thus included in our meta-analysis, representing 3483 women without endometrial cancer and 330 women with endometrial cancer. TABULATION, INTEGRATION, AND RESULTS: The median endometrial thickness in women with endometrial cancer was 3.7 times that in unaffected women at the same center, and with the same menopausal status and same hormone replacement therapy use category. The detection rate was 63% (95% confidence interval 58, 69) for a 10% false-positive rate, or 96% (95% confidence interval 94, 98) for a 50% false-positive rate. CONCLUSION: Endometrial thickness measurement in symptomatic women does not reduce the need for invasive diagnostic testing because 4% of the endometrial cancers would still be missed with a false-positive rate as high as 50%.

3
UI - 11858901
AU - Kaleli S; Calay Z; Altinok T; Kosebay D
TI - Endometrial mixed Mullerian tumor with heterologous elements following tamoxifen therapy for breast cancer: a case report and literature review.
SO - Eur J Obstet Gynecol Reprod Biol 2002 Mar 10;101(2):204-8
AD - Department of Obstetrics and Gynecology, Cerrahpasa Medical School, Istanbul University, P.O. Box 11, Cerrahpasa, 34000, Istanbul, Turkey. semihkaleli@yahoo.com
CASE: A 67-year-old multiparous woman received 20mg tamoxifen daily for four years after surgical treatment of breast cancer. She presented with vaginal bleeding. Uterine curettage revealed a uterine MMT with heterologous elements. She was treated surgically with adjuvant radiotherapy. Tumor cells were found to be estrogen receptor negative and progesterone receptor positive. Uterine MMT may be linked to long term use of tamoxifen. A mechanism in developing MMT other than estrogen receptor pathway may be possible.

4
UI - 12073048
AU - Kyushima N; Watanabe J; Hata H; Jobo T; Kameya T; Kuramoto H
TI - Expression of cyclin A in endometrial adenocarcinoma and its correlation with proliferative activity and clinicopathological variables.
SO - J Cancer Res Clin Oncol 2002 Jun;128(6):307-12
AD - Department of Obstetrics and Gynecology, Kitasato Medical Institute Hospital, 6-100 Arai, Kitamoto, Saitama 364-8501, Japan.
PURPOSE: Cyclin A is known as an S- and G2-M phase regulatory protein and its abnormal expression has been reportedly implicated in cellular proliferation. This study was designed to investigate the correlation of cyclin A expression with tumorigenesis of the endometrium and clinicopathological variables. METHODS: Immunohistochemical staining using labeled streptavidin-biotin complex was performed on formalin-fixed, paraffin-embedded tissue of normal endometrium (15 cases), endometrial hyperplasia (23 cases), and endometrial adenocarcinoma (endometrioid type) (112 cases). RESULTS: Immunohistochemistry showed that the nuclei of the cells were positive for cyclin A. In normal endometrium, only proliferative phase was focally positive for cyclin A. Cyclin A was also positive for endometrial hyperplasia. Its expression in hyperplasia was significantly more frequent than that of proliferative phase and less than that of endometrioid adenocarcinoma. The labeling index (LI) of cyclin A in endometrioid adenocarcinoma was 16.3+/-6.9 in well-differentiated, 18.3+/-8.8 in moderately differentiated, and 30.2+/-11.8 in poorly differentiated adenocarcinoma, respectively. Cyclin A expression increased significantly more in high histological grades. The area of squamous metaplasia in endometrioid adenocarcinoma was negative for cyclin A. The LI of cyclin A was positively correlated with that of Ki-67 and cyclin-dependent kinase 2. Cyclin A expression was significantly associated with carcinoma without coexisting endometrial hyperplasia and lymphovascular space involvement (LVSI), but not with FIGO stage, myometrial invasion, lymph node metastasis, estrogen receptor, progesterone receptor, and menopause as well as recurrence. CONCLUSIONS: Cyclin A expression was involved in the progression to malignancy of the endometrium and was correlated with proliferative activity and prognostic features including histological grade, without coexisting endometrial hyperplasia and LVSI.

5
UI - 11928828
AU - Hedbla B; Merlo J; Manjer J; Engstrom G; Berglund G; Janzon L
TI - Incidence of cardiovascular disease, cancer and death in postmenopausal women affirming use of hormone replacement therapy.
SO - Scand J Public Health 2002;30(1):12-9
AD - Department of Community Medicine, Lund University, Malmo University Hospital, Malmo, Sweden. Bo.Hedblad@smi.mas.lu.se
AIM: The goal of this study was to evaluate the incidence of myocardial infarction, cancer and death in relation to use of hormone replacement therapy (HRT). METHODS: Nine years' follow up of an urban cohort of peri-/postmenopausal women was undertaken. Local and national registers were used for retrieval of events. RESULTS: The incidence of myocardial infarction per 1.000 person-years in users and non-users was 0.61 (5/962) and 2.20 (92/4759) respectively, adjusted relative risk (RR) 0.37; 95% confidence interval 0.15-0.90. Rates of mortality from cardiovascular disease and cancer were 0.36 and 1.10, p= 0.058, and 2.60 and 2.09, p=0.360 respectively. In terms of all-cause mortality the adjusted RR was 1.02; 0.69-1.52, incidence of cancer 1.28; 1.01-1.64, breast cancer 1.52; 1.01-2.28 and endometrial cancer 3.61; 1.54-8.46. CONCLUSIONS: Women affirming use of HRT had a lower incidence of myocardial infarction. Further studies are needed to assess whether the absence of effect on total mortality may be accounted for by an increased cancer risk.

6
UI - 11933681
AU - Irvin WP; Rice LW; Berkowitz RS
TI - Advances in the management of endometrial adenocarcinoma. A review.
SO - J Reprod Med 2002 Mar;47(3):173-89; discussion 189-90
AD - Division of Gynecologic Oncology, University of Virginia Health System, Charlottesville, VA 22908, USA. wpi9d@hscmail.mcc.virginia.edu
Endometrial adenocarcinoma is the most common and curable gynecologic neoplasm; the five-year survival for women with surgical stage I disease ranges from 83% to 93%; stage II, 73%; stage III, 52%; and stage IV, 27%. The absence of an asymptomatic latency phase amenable to detection through screening and the already excellent cure rates seen with early-stage disease have precluded the need for endometrial cancer screening programs. Adenocarcinomas constitute 97% of endometrial cancers, with endometrioid the most common histologic subtype. Two different pathways of endometrial carcinogenesis exist. One arises in a background of estrogen excess, giving rise to atypical hyperplasia as the malignant precursor of the more common endometrioid adenocarcinomas. The use of oral contraceptives has consistently been shown to decrease the risk of developing endometrial carcinoma via this pathway, with 12 months or more of continuous use decreasing the lifetime risk by 40-50%. The alternate pathway of endometrial carcinogenesis represents malignant transformation of atrophic endometrium and proceeds through endometrial intraepithelial carcinoma as the malignant precursor of the more virulent serous papillary and clear cell endometrial adenocarcinomas. The staging of endometrial cancer (according to the International Federation of Obstetrics and Gynecology) is surgical. Recent studies suggest a therapeutic benefit associated with extensive retroperitoneal lymph node evaluation to determine the disease extent and thereby more effectively direct potentially life-saving adjuvant therapy. Adjuvant radiation therapy, known to have survival benefit in advanced-stage disease, may also have survival benefit in intermediate-risk surgical stage I disease on the basis of results recently released from a Gynecologic Oncology Group study. The use of radiation therapy, systemic chemotherapy and hormonal therapy, alone or in combination, is recommended for primary advanced and recurrent disease.

7
UI - 12006564
AU - Tamura M; Sebastian S; Yang S; Gurates B; Ferrer K; Sasano H; Okamura K;
TI - Bulun SE Up-regulation of cyclooxygenase-2 expression and prostaglandin synthesis in endometrial stromal cells by malignant endometrial epithelial cells. A paracrine effect mediated by prostaglandin E2 and nuclear factor-kappa B.
SO - J Biol Chem 2002 Jul 19;277(29):26208-16
AD - Department of Obstetrics and Gynecology and Molecular Genetics, the University of Illinois, Chicago, Illinois 60612, USA.
We investigated the regulation of prostaglandin production in normal endometrial stromal cells (ESC) by malignant endometrial epithelial cells. We found that cyclooxygenase (COX)-2 mRNA and protein levels and prostaglandin (PG)E(2) production in ESC were significantly increased by Ishikawa malignant endometrial epithelial cell conditioned medium (MECM). By using transient transfection assays, we found that the -360/-218-bp region of the COX-2 promoter gene was critical for MECM induction of promoter activity. This MECM-responsive region contained a variant nuclear factor (NF)-kappa B site at -222 to -213 that, when mutated, completely abolished COX-2 promoter activation by MECM. Employing electrophoretic mobility shift assays, we further demonstrated that binding of NF-kappa B p65 to this NF-kappa B-binding site is, in part, responsible for the COX-2 promoter activation by MECM. To investigate further the potential effects of MECM on COX-2 mRNA stability, ESC were treated with MECM in the absence or presence of actinomycin D, a general transcription inhibitor. We found that MECM significantly increased COX-2 mRNA stability. Intriguingly, we found that PGE(2) was one of the major factors in MECM, which was responsible for up-regulating COX-2 expression in ESC. ECC-1 and HEC-1A malignant endometrial epithelial cell lines also produced significantly increased quantities of PGE(2). In conclusion, malignant endometrial epithelial cells secrete PGE(2) that induces COX-2 expression in normal endometrial stromal cells in a paracrine fashion through activation of transcription and stabilization of COX-2 mRNA.

8
UI - 12147433
AU - Terry PD; Rohan TE; Franceschi S; Weiderpass E
TI - Cigarette smoking and the risk of endometrial cancer.
SO - Lancet Oncol 2002 Aug;3(8):470-80
AD - Department of Epidemiology and Social Medicine at the Albert Einstein College of Medicine, Bronx, NY 10461, USA. pterry@aecom.yu.edu
Epidemiological studies have shown that cigarette smoking is associated with a reduced risk of endometrial cancer, in contrast to the increased risks observed with many other non-respiratory-tract cancers, including those of the bladder, pancreas, and cervix uteri. Some studies of endometrial cancer suggest that the inverse association with smoking is limited to certain groups of women, such as those who are postmenopausal or those taking hormone-replacement therapy. The biological mechanisms that might underlie this association remain unclear, although several have been proposed, including an antioestrogenic effect of cigarette smoking on circulating oestrogen concentrations, a reduction in relative bodyweight, and an earlier age at menopause. We have examined the evidence for an association between cigarette smoking and risk of endometrial cancer, including studies related to the proposed biological mechanisms.

9
UI - 10934963
AU - Shidham VB; Dayer AM; Basir Z; Kajdacsy-Balla A
TI - Cervical cytology and immunohistochemical features in endometrial adenocarcinoma simulating microglandular hyperplasia. A case report.
SO - Acta Cytol 2000 Jul-Aug;44(4):661-6
AD - Department of Pathology, Medical College of Wisconsin, Milwaukee 53226, USA. vshidham@mcw.edu
BACKGROUND: The histology of a few cases of adenocarcinoma simulating cervical microglandular hyperplasia (MGH-AdCa) has been reported. However, the cytologic features of MGH-AdCa in cervical smears and the immunohistochemical profile have not been described. CASE: A 73-year-old female presented with vaginal bleeding. The cervical Pap smear was initially interpreted by the cytotechnologist as "reactive endocervical cells" and was referred for cytopathologist review. The final interpretation was atypical glandular cells of undetermined significance (AGUS), probably neoplastic. Endometrial biopsy and total abdominal hysterectomy with bilateral salpingo-oophorectomy showed International Federation of Gynecologists and Obstetricians grade 1 endometrial carcinoma. The superficial component of the tumor resembled cervical microglandular hyperplasia (MGH); the deeper component had an endometrioid pattern. The Pap smear predominantly showed a glandular component with features of MGH. However, the presence of scattered single cells with hyperchromatic nuclei, one to three nucleoli, easily detectable mitotic figures, randomly scattered apoptotic bodies and focal, watery diathesis suggested a neoplastic process. Immunohistochemistry was studied on paraffin sections. In addition to other markers, the tumor cells were immunoreactive for carcinoembryonic antigen (CEA). CONCLUSION: Although the cervical Pap smear in this case had an MGH-like pattern, some features were atypical enough to suggest a diagnosis of AGUS, probably neoplastic. CEA immunoreactivity of MGH-AdCa could also help to differentiate it from MGH.

10
UI - 10976693
AU - Lax SF; Kurman RJ; Pizer ES; Wu L; Ronnett BM
TI - A binary architectural grading system for uterine endometrial endometrioid carcinoma has superior reproducibility compared with FIGO grading and identifies subsets of advance-stage tumors with favorable and unfavorable prognosis.
SO - Am J Surg Pathol 2000 Sep;24(9):1201-8
AD - Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
The International Federation of Gynecology and Obstetrics (FIGO) grading of uterine endometrial endometrioid carcinoma requires evaluation of histologic features that can be difficult to assess, including recognition of small amounts of solid growth, distinction of squamous from nonsquamous solid growth, and assessment of degree of nuclear atypia. The authors describe a novel, binary architectural grading system that uses low-magnification assessment of amount of solid growth, pattern of invasion, and presence of necrosis to divide endometrioid carcinomas into low- and high-grade tumors. The authors analyzed its performance for predicting prognosis and with respect to intra- and interobserver reproducibility. A total of 141 endometrioid carcinomas from hysterectomy specimens were graded according to the FIGO system, nuclear grading, and the binary architectural system. A tumor was classified as high grade if at least two of the following three criteria were present: (1) more than 50% solid growth (without distinction of squamous from nonsquamous epithelium); (2) a diffusely infiltrative, rather than expansive, growth pattern; and (3) tumor cell necrosis. For tumors that were confined to the endometrium, only percent solid growth and necrosis were evaluated, and those with both solid growth of more than 50% and necrosis were considered high grade. All tumors were graded independently by three pathologists on two separate occasions. Both inter- and intraobserver agreement using the binary grading system (kappa = 0.65 and 0.79) were superior compared with FIGO (kappa = 0.55 and 0.67) and nuclear grading (kappa = 0.22 and 0.41). The binary grading system stratified patients into three distinct prognostic groups. Patients with stage I low-grade tumors with invasion confined to the inner half of the myometrium (stages IA and IB) had a 100% 5-year survival rate. Patients with low-grade tumors that invaded beyond the outer half of the myometrium (stage IC and stages II-IV) and those with high-grade tumors with invasion confined to the myometrium (stages IB and IC) had a 5-year survival rate of 67% to 76%. In striking contrast to patients with advance-stage low-grade tumors, patients with advance-stage high-grade tumors had a 26% 5-year survival rate. This binary grading system has advantages over FIGO and nuclear grading that permit greater interobserver and intraobserver reproducibility and should be tested in other studies of endometrial endometrioid carcinomas to validate its reproducibility and use for segregating patients into different prognostic groups.

11
UI - 11431710
AU - Matias-Guiu X; Catasus L; Bussaglia E; Lagarda H; Garcia A; Pons C;
TI - Munoz J; Arguelles R; Machin P; Prat J Molecular pathology of endometrial hyperplasia and carcinoma.
SO - Hum Pathol 2001 Jun;32(6):569-77
AD - Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.
Four different genetic abnormalities may occur in endometrioid adenocarcinomas of the endometrium (mircosatellite instability and mutations in the PTEN, k-RAS and beta-catenin genes), whereas nonendometrioid carcinomas of the endometrium often have p53 mutations and loss of heterozygosity on several chromosomes. Occasionally, a nonendometrioid carcinoma may develop as a result of dedifferentiation of a preexisting endometrioid carcinoma; in such a case, the tumor exhibits overlapping clinical, morphologic, immunohistochemical, and molecular features of the 2 types. The insaturation of microsatellite instability in endometrial carcinogenesis seems to occur late in the transition from complex hyperplasia to carcinoma, and it is preceded by progressive inactivation of MLH-1 by promoter hypermethylation. Moreover, the endometrioid adenocarcinomas that exhibit microsatellite instability show a stepwise progressive accumulation of secondary mutations in oncogenes and tumor suppressor genes that contain short-tandem repeats in their coding sequences. Mutations in the PTEN and k-RAS genes are also frequent in endometrioid adenocarcinomas of the endometrium, particularly in the tumors that exhibit microsatellite instability, whereas beta-catenin mutations do not seem to be associated with such a phenomenon. Copyright 2001 by W.B. Saunders Company.

12
UI - 11876387
AU - Renard F; Vosse M; Scagnol I; Verhest A
TI - Aggressive endometrial carcinoma in a breast cancer patient treated with tamoxifen with normal transvaginal ultrasonography. Case report.
SO - Eur J Gynaecol Oncol 2002;23(1):25-8
AD - Data Centre, Jules Bordet Institute, Brussels, Belgium.
Since tamoxifen therapy can induce endometrial disorders, surveillance schemes of women taking tamoxifen have been recommended. Transvaginal ultrasonography is a very sensitive test and therefore is often performed as a first-line screening test. We described a very atypical case of a high stage, high grade endometrial cancer associated with tamoxifen in a 64-year-old woman with a past history of breast cancer. This women was assessed yearly by ultrasonography and Pap smear. The cancer developed on a very thin endometrium and transvaginal ultrasonography failed to detect it. The patient remained asymptomatic up to the diagnosis. Normal endometrial cells in the Pap smear test were the only signs associated with this cancer. Surveillance strategies and significance of endometrial cells on the Pap smear are reviewed. In conclusion, TVUS can fail to detect cancers if the endometrial lining is not enlarged. In case of normal endometrial cells in the Pap smear, a careful evaluation should be performed.

13
UI - 11876394
AU - Holub Z; Jabor A; Kliment L
TI - Comparison of two procedures for sentinel lymph node detection in patients with endometrial cancer: a pilot study.
SO - Eur J Gynaecol Oncol 2002;23(1):53-7
AD - Department of Obstetrics and Gynaecology, Endoscopic Training Centre, Baby Friendly Hospital, Kladno, Czech Republic.
OBJECTIVE: The purpose of this study was to assess the feasibility and contribution of two intraoperative procedures of lymphatic mapping and sentinel node detection using a blue dye in surgically-staged patients with early stage endometrial cancer. METHODS AND MATERIALS: In 25 cases of endometrial cancer, patent blue-V was injected into the subserosal myometrium (13 cases, SM group) or cervico-subserosal myometrium (12 cases, CSM group) during a surgical staging procedure. Laparoscopically-assisted vaginal hysterectomy and pelvic lymphadenectomy were completed successfully in 23 women out of 24 laparoscopically-staged patients (95.8%). One patient with FIGO stage IIa was indicated for a radical abdominal surgery. RESULTS: A deposition of the blue dye was found in at least one pelvic lymph node (LN) in eight out of 13 cases (61.5%) in the SM group compared with ten out of 12 cases (83.3%) in the CSM group (p = 0.378). The mean number of dye-colored LN (DCLN) was 1.15 (SM group) and 2.5 (CSM group), respectively (p = 0.05). The rate of DCLN/LN was 15/188 (SM group) versus 30/190. respectively (p = 0.03). An uptake of the blue bye was observed in a total of 45 out of 388 LN. CONCLUSION: An intraoperative combination of cervico-subserosal myometrium application of the blue dye allows successful detection (83.3%) of sentinel LN in patients with endometrial cancer. Comparing SM and CSM groups the statistical significant difference was found in the DCLN/LN rate and mean number of sentinel lymph nodes (p = 0.03, p = 0.05, respectively). Clinical validity of this surgical procedure must be assessed prospectively.

14
UI - 11876395
AU - Yalman D; Arican A; Ozsaran Z; Celik OK; Yurut V; Esassolak M;
TI - Haydaroglu A Evaluation of morbidity after external radiotherapy and intracavitary brachytherapy in 771 patients with carcinoma of the uterine cervix or endometrium.
SO - Eur J Gynaecol Oncol 2002;23(1):58-62
AD - Ege University, Faculty of Medicine, Department of Radiation Oncology, Izmir, Turkey.
PURPOSE: The aim of the present study was to evaluate early and late radiation morbidity and to assess the factors influencing morbidity in patients with cervical or endometrial cancer treated by a combination of external radiotherapy (ERT) and intracavitary brachytherapy (IBRT). MATERIALS AND METHODS: Early and late radiation morbidity were evaluated retrospectively using RTOG/EORTC criteria and Franco-Italian glossary in Four hundred and seven patients (52.8%) had endometrial carcinoma and 364 (47.2%) had carcinoma of the cervix. One hundred and fifty-four patients with cervical carcinoma were inoperable. In patients with endometrial carcinoma total doses at the vagina, bladder and rectum were 60.36 Gy, 56.2 Gy and 55.6 Gy respectively. Biologically equivalent doses (BED) for the same points were 79.35, 68.63 and 67.37, respectively for early effects and 123.67, 97.65 and 94.85, respectively for late effects. One hundred and sixty-nine patients (41.5%) developed acute morbidity, grade I and II bladder morbidity being the most common type and 85 patients (20.9%) developed late morbidity, grade I and II vaginal morbidity being the most common type. No grade IV morbidity was recorded. Total doses at the vagina, bladder and rectum in operated cervix cancer patients were 60.51 Gy, 56.53 Gy and 55.67 Gy, respectively. BED for the same points were 79.77, 69.36 and 67.52, respectively for early effects and 124.74, 99.3 and 95.17, respectively for late effects. Eighty patients (38.1%) developed early morbidity. Grade I and II bladder morbidity was the most common type. Sixty-five patients (30.9%) developed late morbidity, vaginal morbidity being the most common type. Total doses at the vagina, bladder and rectum in inoperable patients were 70.92 Gy, 66.71 Gy and 62.38 Gy, respectively. BED for the same points were 97.43, 89.64 and 81.63, respectively for early effects and 159.3, 143.16 and 126.56, respectively for late effects. Sixty patients (39%) developed acute morbidity which was grade I or II bladder morbidity in 95%. Ninety-five patients (61.7%) developed late morbidity which was grade I-III vaginal morbidity in 94%. CONCLUSION: Patients with cervical or endometrial cancer can be treated safely by a combination of ERT and IBRT. However the patients should be assessed before, during and after treatment and at every period of follow-up using a standard and well-defined system in order to define and predict the morbidity rate.

15
UI - 11876398
AU - Kondi-Pafiti A; Kairi-Vassilatou E; Frangou-Plemenou M; Dimopoulou C;
TI - Englezou M; Sykiotis K Immunohistochemical investigation of p-53, C-NEU and EGFR expression in HPV-related epidermoid endometrial carcinoma.
SO - Eur J Gynaecol Oncol 2002;23(1):70-1
AD - Pathology Department, Areteion Hospital, Athens University, Greece.
Epidermoid carcinoma (PSCC) of the endometrium is a rare form of endometrial cancer that constitutes about 0.1% of all malignant epithelial tumors of the uterus. The diagnosis of PSCC is based on strict criteria and is made in the absence of a glandular component of the tumor. Squamous cell carcinoma of the endometrium should enter the differential diagnosis in postmenopausal patients in the presence of atypical squamous cells in the uterine curettage, while the cervical biopsies are negative for malignancy. The presence of HPV should be investigated as well, so that its pathogenetic relation is clarified. While no significant relation was found to p-53, C-NEU and EGFR expression this investigation must be continued because. HPV may interact with tumor suppressor genes.

16
UI - 11876399
AU - Uzunlar AK; Yilmaz F; Kilinc N; Arslan A
TI - Cavernous hemangioma of the uterus (a case report).
SO - Eur J Gynaecol Oncol 2002;23(1):72-3
AD - Department of Pathology, Dicle University, Faculty of Medicine, Diyarbakir, Turkey.
Cavernous hemangioma of the uterus is an extremely rare lesion. We report a postmenopausal patient with abnormal uterine bleeding due to hemangioma and simple endometrial hyperplasia.

17
UI - 12184043
AU - Porter S
TI - Endometrial cancer.
SO - Semin Oncol Nurs 2002 Aug;18(3):200-6
AD - Hope-A Women's Cancer Center, Asheville, NC, USA.
OBJECTIVES: To provide an update for nurses involved in the care of women at risk or being treated for endometrial cancer. DATA SOURCES: Review articles, research reports, and medical and nursing text-books. CONCLUSIONS: Endometrial cancer is the most common gynecologic malignancy. Although most women with endometrial cancer present with early stage disease and have an excellent chance of cure, approximately 6,600 women in the United States are expected to die from the disease in 2002. Treatment of patients with advanced or recurrent disease remains challenging, with no proven best standard of treatment. IMPLICATIONS FOR NURSING PRACTICE: Nursing plays an important role in prevention and early detection of endometrial cancer, patient education, patient care, and rehabilitation.

18
UI - 12177772
AU - Otsuka I; Kubota T; Aso T
TI - Lymphadenectomy and adjuvant therapy in endometrial carcinoma: role of adjuvant chemotherapy.
SO - Br J Cancer 2002 Aug 12;87(4):377-80
AD - Department of Obstetrics and Gynecology, Tokyo Medical and Dental University Hospital 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. i.otsuka.gyne@tmd.ac.jp
To evaluate the therapeutic benefit of lymphadenectomy and adjuvant therapy, in particular chemotherapy, we retrospectively analysed survival rates and patterns of recurrence of endometrioid adenocarcinoma in 106 patients who underwent surgery including retroperitoneal lymphadenectomy. Adjuvant chemotherapy was administered to 46 patients (42 received a platinum-based regimen) and pelvic irradiation to 12. The 5-year survival rate of 23 patients with lymph node metastasis was worse than that of patients without lymph node metastasis (60% vs 96%, P<0.0001). Recurrence was observed in 14 patients (10 patients with chemotherapy, two with irradiation, and two without adjuvant therapy); the first site of recurrence was in distant sites in 12 patients; recurrence in the pelvic sidewall or exclusively in lymph nodes was not observed. The 5-year survival rate of 18 patients with lymph node metastasis treated with chemotherapy, was 61% including all 14 with macroscopically positive nodes and all nine with paraaortic metastasis. Of seven patients with bulky positives nodes, three patients with bulky paraaortic nodes died of the disease, three of the four patients with bulky pelvic but without bulky paraaortic nodes had no recurrence. In summary, lymphadenectomy may afford a survival benefit via the debulking of macroscopically positive nodes, and the predominance of distant recurrences suggests that chemotherapy is a suitable choice as an adjuvant therapy in endometrial carcinoma after lymphadenectomy.

19
UI - 12214463
AU - Katsumata N; Yamanaka Y; Kitagawa R
TI - [Latest information of therapeutic approach for endometrial cancer]
SO - Gan To Kagaku Ryoho 2002 Aug;29(8):1371-6
AD - Department of Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
The role of chemotherapy for metastatic endometrial carcinoma is palliation, although modest response can be achieved because of development of chemotherapy. The response rate is 31-56% of conventional CAP therapy and 33-81% of AP therapy. However these chemotherapeutic regimen did not prolong the survival. Recently, a randomized trial of TAP therapy (TXL 160 mg/m2 3 h, day 2, ADM 45 mg/m2, day 1, CDDP 50 mg/m2 day 1) versus AP therapy (ADM 60 mg/m2, CDDP 50 mg/m2) was reported. The response and survival of TAP is superior to that of AP. Taxane will be key drugs for chemotherapy of endometrial cancer in the future.

20
UI - 12174957
AU - Scholz HS; Lax S; Petru E; Benedicic C; Winter R
TI - Inguinal lymph node metastasis as the presenting symptom of endometrial cancer: a case report.
SO - Anticancer Res 2002 Jul-Aug;22(4):2531-2
AD - The Department of Obstetrics and Gynecology, University of Graz, Austria. scholzhs@kfunigraz.ac.at
BACKGROUND: Less than 5% of patients with endometrial cancer present with stage IV disease and among these inguinal metastasis is rare. CASE: A 54-year-old patient presented with a palpable, 5x3 cm right inguinal mass. Histopathology showed bulky lymph nodes with mucinous adenocarcinoma. Hysteroscopy and curettage revealed well-differentiated endometrioid adenocarcinoma. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and systematic pelvic and paraaortic lymphadenectomy were performed. Final histopathology showed an endometrioid adenocarcinoma with infiltration of the inner half of the myometrium. Metastases up to 2.3 cm in diameter were found in 11 out of 76 pelvic, and 17 out of 51 paraaortic lymph node CONCLUSION: Inguinal lymph node metastasis can occur in patients with endometrial cancer and may be the presenting symptom in patients with occult endometrial disease.

21
UI - 12209691
AU - Sivridis E; Giatromanolaki A; Gatter KC; Harris AL; Koukourakis MI;
TI - Tumor and Angiogenesis Research Group Association of hypoxia-inducible factors 1alpha and 2alpha with activated angiogenic pathways and prognosis in patients with endometrial carcinoma.
SO - Cancer 2002 Sep 1;95(5):1055-63
AD - Department of Pathology, Democritus University of Thrace, Alexandroupolis, Greece.
BACKGROUND: Hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha are essential regulatory proteins for the adaptation of tumor cells to hypoxia, and they stimulate angiogenesis through activation of the vascular endothelial growth factor (VEGF) gene. METHODS: HIF-1alpha and HIF-2alpha proteins were studied immunohistochemically in a group of 81 patients with Stage I endometrial adenocarcinoma of the endometrioid cell type. The results were correlated with intratumoral angiogenesis, the expression of the angiogenic factors VEGF and thymidine phosphorylase (TP), and the VEGF/receptor (VEGF/KDR) complex. Relations also were sought with estrogen receptor (ER) and progesterone receptor (PR), with the apoptosis-related proteins bcl-2 and p53, with several histopathologic parameters, and with patient prognosis. In addition, a sample of 25 normal endometria at various phases of the menstrual cycle was studied for the presence of HIF-1alpha and HIF-2alpha. RESULTS: HIF-1alpha expression was detected in 49% of endometrial carcinomas. The expression was cytoplasmic or mixed nuclear/cytoplasmic. HIF-1alpha expression was associated with up-regulation of the VEGF pathway and with increased standard microvessel density (sMVD) and activated VEGF/KDR microvessel density (aMVD). It also was associated with a poor prognosis in both univariate and multivariate analyses. HIF-2alpha protein showed a pattern of expression similar to the pattern seen in HIF-1alpha, but expression of HIF-2alpha protein occurred in only 17% of endometrial carcinomas, and it was associated with increased TP reactivity. There also was a relation of HIF-1alpha expression with well-differentiated endometrial neoplasms, and there was a marginal association of HIF-1alpha and HIF-2alpha with ER expression. With reference to normally cycling tissues, HIF-1alpha nuclear/cytoplasmic expression was particularly strong in the samples of early proliferative phase endometrium compared with HIF-2alpha protein expression, which showed a constant reaction throughout the menstrual cycle. CONCLUSIONS: The up-regulation of HIF-1alpha and, to a lesser extent, of HIF-2alpha is a common event in Stage I endometrial adenocarcinomas. In these tumors, HIF-1alpha expression is related to increased angiogenesis, through activation of the VEGF angiogenic pathway, and to an unfavorable prognosis. HIF-2alpha accumulation is associated with increased expression of the angiogenic factor TP. Copyright 2002 American Cancer Society.

22
UI - 9869450
AU - Li Y; Rinehart CA
TI - Regulation of keratinocyte growth factor expression in human endometrium: implications for hormonal carcinogenesis.
SO - Mol Carcinog 1998 Dec;23(4):217-25
AD - Department of Pathology and Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599-7295, USA.
Estrogen is thought to be an important etiologic agent in endometrial and breast cancers. However, the mechanism or mechanisms by which estrogen acts as a hormonal carcinogen are not well understood. We hypothesize that in response to chronic exposure to estrogens, human endometrial stromal fibroblasts (ESF) produce factors that facilitate neoplastic transformation in epithelial cells. To test this hypothesis, we assessed the regulation of keratinocyte growth factor (KGF) mRNA and protein in ESF by interleukin-1 (IL-1) and diethylstilbestrol (DES). Short-term treatments with IL-1 but not with DES increased the abundance of KGF mRNA in ESF. However, chronic treatment with DES significantly increased KGF mRNA levels and protein production. KGF protein in medium conditioned by ESF chronically treated with 1 nM DES reached concentrations of approximately 100 ng/mL. At this concentration, KGF increased endometrial epithelial cell numbers fourfold and enhanced anchorage independence tenfold. These results suggest that KGF may play a role in hormonal carcinogenesis by mediating estrogen-induced changes in the interactions between stromal and epithelial cells. To address the potential role of nuclear transcription factor kappa B (NF-kappaB) in regulating KGF expression, we determined the effect of increased expression of its inhibitor, IkappaBalpha, on KGF mRNA and protein levels. Transfection with IkappaBalpha blocked induction of KGF expression by IL-1 but had no effect on the increase in KGF mRNA caused by chronic treatment with DES. These results suggest that IL-1 exerts its effects on KGF by an NF-kappaB-mediated pathway but that chronic treatment with DES stimulates KGF expression by some other mechanism.

23
UI - 10383166
AU - Schwartz S Jr; Yamamoto H; Navarro M; Maestro M; Reventos J; Perucho M
TI - Frameshift mutations at mononucleotide repeats in caspase-5 and other target genes in endometrial and gastrointestinal cancer of the microsatellite mutator phenotype.
SO - Cancer Res 1999 Jun 15;59(12):2995-3002
AD - The Burnham Institute, La Jolla, California 92037, USA.
The majority of tumors from hereditary nonpolyposis colorectal cancer families and a subset of unselected gastrointestinal and endometrial tumors exhibit a microsatellite mutator phenotype (MMP) that leads to the accumulation of hundreds of thousands of clonal mutations in simple repeat sequences. The mutated genes with positive or negative roles in cell growth or survival in aneuploid gastrointestinal cancer (e.g., APC, K-ras, and p53) are less frequently mutated in near-diploid MMP gastrointestinal tumors. These tumors accumulate mutations in other genes, such as DNA mismatch repair hMSH3 and hMSH6, transforming growth factor-beta type II receptor, and BAX. All these genes carry, within their coding sequences, mononucleotide repeats that are preferred targets for the MMP. Endometrial carcinoma is the most common type of extracolonic neoplasia in the hereditary nonpolyposis colorectal cancer syndrome, but the spectrum of its target cancer genes is not well characterized. Here, we report that endometrial cancer of the MMP also accumulates mutations in genes that are typically mutated in gastrointestinal cancer of the mutator pathway, including BAX (55%), hMSH3 (28%), and hMSH6 (17%). We also report the detection of frameshift mutations in caspase-5, a member of the caspase family of proteases that has an (A)10 repeat within its coding region, in MMP tumors of the endometrium, colon, and stomach (28, 62, and 44%, respectively). We therefore suggest caspase-5 as a new target gene in the microsatellite mutator pathway for cancer.

24
UI - 10717241
AU - Semba S; Ouyang H; Han SY; Kato Y; Horii A
TI - Analysis of the candidate target genes for mutation in microsatellite instability-positive cancers of the colorectum, stomach, and endometrium.
SO - Int J Oncol 2000 Apr;16(4):731-7
AD - Department of Molecular Pathology, Tohoku University School of Medicine, Aoba-ku, Sendai 980-8575, Japan.
Microsatellite instability (MSI) in human carcinoma DNA is a characteristic phenotype observed in hereditary non-polyposis colorectal cancer and also in some human sporadic cancers including multiple primary carcinomas. In this study, we analyzed mutations in the hCHK1, E2F4, hMSH3, and hMSH6 genes in MSI+ human cancers arising in colorectum, stomach and endometrium. The E2F4 and hMSH3 genes were mutated in all tumor types. Interestingly, the hMSH6 gene was mutated in colorectal and gastric cancers but not in endometrial cancer; this is similar to the TGFbetaRII gene. It is notable that the mutation status of the secondary mutators, hMSH3 and hMSH6, did not influence slippage-related frameshift mutations in genes harboring simple tandem-repeats, which suggests that the MSI phenotype may be affected mainly by abnormalities in the primary mutator genes, not by the secondary mutator genes. No mutations were observed in the cell cycle checkpoint gene hCHK1; mutations of this gene are thought to have a limited role, if any, in at least the tumor types analyzed in this study.

25
UI - 11546830
AU - Liu T; Chen J; Salahshor S; Kuismanen S; Holmberg E; Gronberg H;
TI - Peltomaki P; Lindblom A Screening families with endometrial and colorectal cancers for germline mutations.
SO - J Med Genet 2001 Sep;38(9):E29

26
UI - 12060444
AU - Look K
TI - Stage I-II endometrial adenocarcinoma evolution of therapeutic paradigms: the role of surgery and adjuvant radiation.
SO - Int J Gynecol Cancer 2002 May-Jun;12(3):237-49
AD - Section Gyn-Oncology, Indiana University School of Medicine, 535 Barnhill Drive Room 434, Indianapolis, IN 46202, USA.
The objective was to review the English-language literature regarding the utility of adjuvant radiation therapy following surgery for endometrial adenocarcinoma. An OVID software (Ovid Technologies, Inc., New York, NY) search of Medline articles from 1975 to 2001 was conducted using the keywords "endometrial neoplasm," "surgery," and "radiation therapy." The papers were assessed with regard to (a) extent of surgical staging (b) type of adjuvant radiotherapy utilized: external vs. brachytherapy vs. combination therapy; and (c) whether the patients were treated as part of prospective trial or reported as a descriptive series reflecting an institution's practice pattern. Survival rates are excellent for patients with early stage disease treated in either paradigm of extended-surgical staging with more restricted use of the adjuvant therapy or simple hysterectomy bilateral salpingoophorectomy with more frequent use of adjuvant radiotherapy. All three prospective-randomized trials (PRCT) have shown an improvement in local control but no overall survival benefit for the entire accrued group. All three PRCTs have shown a higher risk of disease recurrence in older patients or those with grade 3 histology or deep invasion. Each suggests there may be a survival benefit for the subset of patients with such high-risk features, but at present there is no prospective data that demonstrates adjuvant radiotherapy will improve the overall survival for the highest-risk subset of older patients with high-grade deeply invasive disease.

27
UI - 12060447
AU - Patai K; Szentmariay IF; Jakab Z; Szilagyi G
TI - Early detection of endometrial cancer by combined use of vaginal ultrasound and endometrial vacuum sampling.
SO - Int J Gynecol Cancer 2002 May-Jun;12(3):261-4
AD - 2nd Department of Obstetrics and Gynecology, Semmelweis University School of Medicine, H-1082 Budapest U1101 ut 78/a, Hungary. kpatai@hotmail.com
With increasing lifespan and decreased incidence of uterine cervical cancer, the importance of the proper and early diagnosis of endometrial cancer has become a demand to gynecology. The objective of the present study is to evaluate the effectiveness of gynecologic diagnostic tools in detection of endometrial cancer in early stage. The patients (72) involved in the study, after giving their informed consent, were investigated by transvaginal ultrasound and subsequent vacuum endometrial sampling in office settings. Whenever the histology examination of endometrial vacuum sampling showed hyperplasia or carcinoma, it was reassured by sampling with dilatation and curettage. The analysis of sonography and histology results showed that in 4 cases (5.6%) endometrial hyperplasia and in two cases (2.8%) endometrial adenocarcinoma were present. Also analyzed were sensitivity, specificity, positive and negative predictive values for histology results and for sonographic findings. These results show that transvaginal ultrasound is a reliable method for screening for endometrial carcinoma. Moreover, in the case of pathologic endometrial change suspected by ultrasound, the combination of vacuum endometrial sampling with ultrasound examination can yield firm diagnosis in office settings, saving cost and time in early diagnosis of endometrial cancer.

28
UI - 12060450
AU - Fanning J; Brown S; Phibbs G; Kramer T; Zaher A
TI - Immunohistochemical evaluation is not prognostic for recurrence in fully staged high-risk endometrial cancer.
SO - Int J Gynecol Cancer 2002 May-Jun;12(3):286-9
AD - Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Richard D. Ruppert Health Center, Medical College of Ohio, 3120 Glendale Avenue, Toledo, OH 43614-5809, USA. jfanning@mco.edu
The objective of this study was to determine the prognostic significance of common immunohistochemical pathologic risk factors in fully staged high-risk endometrial cancers. Sixty-two of 265 consecutive endometrioid adenocarcinomas were considered high risk for recurrence because of deep myometrial invasion and poor differentiation (stage IC, G3), cervical metastasis (stage II), ovarian metastasis (stage IIIA) or lymph node metastasis (stage IIIC). All patients underwent complete

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NCI CANCERLIT^® Search: Endometrial Cancer - September 2002

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