National Cancer Institute®
Last Modified: April 1, 2002
UI - 11228540
AU - Tong BJ; Tan J; Tajeda L; Das SK; Chapman JA; DuBois RN; Dey SK
TI - Heightened expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor-delta in human endometrial adenocarcinoma.
SO - Neoplasia 2000 Nov-Dec;2(6):483-90
AD - Department of Obstetrics and Gynecology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Epidemiological studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) significantly reduce the risk and mortality from colorectal cancer, in part by inhibiting prostaglandin (PG) synthesis. Cyclooxygenase (COX), the rate-limiting enzyme in PG biosynthesis, exists in two isoforms, COX-1 and COX-2. Genetic and pharmacological evidence suggest that COX-2 is involved in the development of colorectal cancer. We have previously shown that COX-2-derived prostacyclin participates in blastocyst implantation through activation of peroxisome proliferator activated receptor delta (PPARdelta), a member of the nuclear hormone receptor family. Furthermore, our recent studies suggest that a similar pathway is operative during colorectal carcinogenesis. These observations prompted us to examine whether the COX-2-PPARdelta signaling pathway is also involved during development of uterine adenocarcinoma. Here we describe for the first time the heightened expression of COX-2 and PPARdelta, but not COX-1, in uterine endometrial adenocarcinoma.
UI - 11894549
AU - Marcy PY; Largillier R; Bailet C; Hannoun-Levi JM; Magne N
TI - [132 grams of tamoxifen: ultrasonographic and MRI appearance of endometrial carcinoma]
SO - J Radiol 2001 Nov;82(11):1633-6
AD - Service de Radiologie, Centre Antoine Lacassagne, 33 avenue de Valombrose, 06189 Nice. email@example.com
Endometrial carcinoma is a rare iatrogenic complication due to the adverse estrogenic like effect of Tamoxifen on the uterine mucosa. We report the delayed case of an endometrial carcinoma after an unusual twleve year long daily administration of Tamoxifen (cumulative dose = 131 g). Endovaginal contrast ultrasound examination (Levovist, Schering, Germany) and MRI appearances are described.
UI - 11781517
AU - McCluggage WG; Sumathi VP; McBride HA; Patterson A
TI - A panel of immunohistochemical stains, including carcinoembryonic antigen, vimentin, and estrogen receptor, aids the distinction between primary endometrial and endocervical adenocarcinomas.
SO - Int J Gynecol Pathol 2002 Jan;21(1):11-5
AD - Department of Pathology, Royal Group of Hospitals Trust, Belfast, Northern Ireland.
The histological distinction between a primary endometrial and a primary endocervical adenocarcinoma is often difficult, especially in small biopsy specimens. A preoperative distinction is important because primary surgical management differs between the two tumors. Cases of primary endometrioid endometrial (n=30) and primary endocervical (n=26) adenocarcinoma of endocervical type were stained immunohistochemically with the monoclonal antibodies against carcinoembryonic antigen (CEA), vimentin, estrogen receptor (ER), and 34 beta E12. In all cases the origin of the adenocarcinoma was confirmed by examination of the definitive pathology specimen. There was diffuse positive nuclear staining for ER in 28 of 30 (93%) endometrial adenocarcinomas. ER was negative in 16 of 26 endocervical adenocarcinomas, and there was focal weak nuclear staining in the other cases. Vimentin was positive in 29 of 30 (97%) endometrial adenocarcinomas but in only 2 of 26 (8%) endocervical adenocarcinomas. CEA was positive in 25 of 26 (96%) endocervical adenocarcinomas, mostly with diffuse membranous and cytoplasmic staining. Positivity with CEA was present in 21 of 30 (70%) endometrial adenocarcinomas but was largely confined to squamoid areas with only 12 tumors exhibiting focal membranous staining of the glandular component. 34 beta E12 was diffusely positive in all except one cervical adenocarcinoma. In endometrial carcinomas, positivity was strongest in squamoid areas but there was positive staining, either focally or diffusely, of the glandular component in 27 cases. In summary, primary endometrioid endometrial adenocarcinomas are characterized by diffuse, strong, positive staining for vimentin and ER and negative or very focal, positive staining of the glandular component for CEA. In contrast, primary endocervical adenocarcinomas are characterized by CEA positivity, which is usually but not always diffuse, negativity for vimentin, and negativity or focal weak positivity for ER. 34 beta E12 is of no value in the distinction between endometrial and endocervical adenocarcinomas. A panel of immunohistochemical stains, comprising CEA, vimentin, and ER, generally allows confident preoperative distinction between a primary endometrial and endocervical adenocarcinoma.
UI - 11781520
AU - Orbo A; Eklo K; Kopp M
TI - A semiautomated test for microsatellite instability and its significance for the prognosis of sporadic endometrial cancer in northern Norway.
SO - Int J Gynecol Pathol 2002 Jan;21(1):27-33
AD - Department of Clinical Pathology, Institute of Medical Biology, Medical Faculty, University of Tromso, Norway.
Archival histologic material from 105 women (median age 62 years) treated for endometrial cancer was investigated for the replication error phenotype indicated by the observation of widespread microsatellite instability (MSI). Polymerase chain reaction (PCR) of DNA isolated from paraffin-embedded tissue was analyzed for MSI using six microsatellite loci with a fluorescent-based detection system. Flow cytometry and morphometric investigation were performed in the same material for each of the patients. Twenty percent (21 of 105) of screened endometrial cancers were found to have high MSI at two or more of the loci tested. The mean detection frequency per marker was highest in the dinucleotide repeat sequence, D2S123, and the mononucleotide repeat sequences amplified by Bat 25 and Bat 26. Death from endometrial cancer was not related to the occurrence of MSI (p=0.6). There was no significant association between MSI and FIGO stage (p=0.5), myometrial invasion depth (p=0.8), histological grade (p=0.3), or vessel invasion (p=0.5). There were, however, more MSI cases among the group of diploid cases compared with the aneuploid and tetraploid group. MSI is not a valuable prognosticator for survival of sporadic endometrial cancer, and diploid cases are significantly more often MSI positive than aneuploid and tetraploid cases.
UI - 11781516
AU - Castrillon DH; Lee KR; Nucci MR
TI - Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study.
SO - Int J Gynecol Pathol 2002 Jan;21(1):4-10
AD - Women's and Perinatal Pathology Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
We investigated the possibility of distinguishing between primary endometrial and endocervical adenocarcinomas by using a panel of immunohistochemical stains, which included vimentin (VIM), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratins 7 and 20 (CK7 and CK20). Twenty-nine endocervical adenocarcinomas (CCAs) and 30 endometrial adenocarcinomas (EMCAs) including cases with overlapping histologic features (CCAs with endometrioid differentiation [15/29] and EMCAs with mucinous differentiation [16/30]) were evaluated. Most EMCAs (29/30, 97%) were VIM positive, whereas only 2/29 (7%) CCAs were VIM positive. The great majority of EMCAs (28/30) and all 29 CCAs were CK7 positive, whereas all 30 EMCAs and 27/29 CCAs were negative for CK20. CEA positivity was more common in CCAs (18/29, 62%) than in EMCAs (8/30, 27%). EMA positivity was present in all 30 EMCAs and in 26 of 29 (90%) CCAs. We conclude that VIM and CEA are useful immunohistochemical markers in distinguishing EMCAs and CCAs, but CK7, CK20, and EMA are not useful in this distinction.
UI - 11781523
AU - Oliva E; Clement PB; Young RH
TI - Epithelioid endometrial and endometrioid stromal tumors: a report of four cases emphasizing their distinction from epithelioid smooth muscle tumors and other oxyphilic uterine and extrauterine tumors.
SO - Int J Gynecol Pathol 2002 Jan;21(1):48-55
AD - James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Three endometrial and one extrauterine endometrioid stromal tumors (three sarcomas and one stromal nodule) with a prominent component of epithelioid cells with abundant eosinophilic cytoplasm are described. The patients were 39, 48, 56 and 86 years of age. The endometrial sarcomas were described grossly as an ill-defined tan nodule and "ragged and papillary," respectively, and had the typical infiltrative pattern of low-grade endometrial stromal sarcoma. The stromal nodule was a 13-cm, well circumscribed, yellow, fleshy mass. The extrauterine tumor was probably primary in the sigmoid colon. Oval to polygonal epithelioid cells with abundant eosinophilic cytoplasm accounted for 50% to 90% of the tumor cells. The cytoplasm was granular in one case. None of the tumors contained cells with a rhabdoid appearance. Nuclear and other features did not differ from those of usual endometrial-endometrioid stromal tumors except in one case in which there was greater nuclear pleomorphism. There was strong diffuse cytoplasmic immunoreactivity of all four tumors for vimentin and for CD10 in three of three tumors tested, as well as extensive and moderate reactivity for NK1/C3 and focal weak reactivity for CD68 in two of three tumors tested. Muscle actin positivity was very focal to extensive and weak to strong in all three tumors tested, mainly in the epithelioid areas; alpha-smooth muscle actin was focally to extensively positive in the epithelioid areas of two of three tumors tested; and focal strong desmin positivity (interpreted as indicating smooth muscle metaplasia) was found in the epithelioid areas of one of four tumors. A vaginal recurrence in one case had similar cytologic features to the primary tumor but when examined initially in the absence of adequate history posed diagnostic difficulty, as did evaluation of the uterine tumor in two other cases and the extrauterine tumor in the final case. The differential in these cases is primarily with an epithelioid smooth muscle tumor when they are uterine primaries. The typical infiltration facilitates this distinction in the cases of endometrial stromal sarcomas, but this feature is usually only evident in hysterectomy specimens. In limited samples such as biopsy or curettage specimens, and in some cases of recurrent tumor, awareness that endometrial-endometrioid stromal tumors can have epithelioid cells is crucial in the formulation of the differential diagnosis. Diverse oxyphilic tumors, including deciduoid malignant mesothelioma, can potentially be in the differential diagnosis with extrauterine (endometrioid) stromal sarcomas with epithelioid cells. Immunohistochemical evaluation may potentially provide major aid in diagnosis.
UI - 11801878
AU - Latta E; Chapman WB
TI - PTEN mutations and evolving concepts in endometrial neoplasia.
SO - Curr Opin Obstet Gynecol 2002 Feb;14(1):59-65
AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Several recent advances have been made in our understanding of the pathogenesis of endometrial tumours, particularly endometrioid endometrial carcinoma (EEC). Mutations in the PTEN gene and microsatellite instability (MSI) are common genetic abnormalities in EECs, and distinguish these lesions from other histological subtypes of endometrial carcinoma. Endometrial precancers are monoclonal lesions that share a common genetic lineage with invasive EEC, including PTEN mutations and MSI. Mutations of the PTEN tumour suppressor gene have been identified in histologically normal-appearing endometrium exposed to oestrogen, 18-55% of endometrial precancers and 26-80% of EECs. PTEN has been shown to play several roles in tumour suppression, including cell cycle arrest and promotion of apoptosis. Loss of PTEN function predisposes endometrial cells to neoplastic transformation, particularly in high-oestrogenic states. MSI is another common alteration seen in EECs and endometrial precancers, and some studies have reported an association between MSI and PTEN mutations. The replication error that results in MSI may facilitate the development of PTEN mutations in some, but not all, cases of EEC. The prognostic significance of PTEN gene mutations and MSI in endometrial carcinoma is controversial. Further study is needed to delineate the different pathogenetic pathways of EEC and their natural history.
UI - 11801879
AU - Elit L; Hirte H
TI - Current status and future innovations of hormonal agents, chemotherapy and investigational agents in endometrial cancer.
SO - Curr Opin Obstet Gynecol 2002 Feb;14(1):67-73
AD - Division of Gynecologic Oncology, MacMaster University, Hamilton, Ontario, Canada. firstname.lastname@example.org
The median survival of women with advanced or recurrent endometrial cancer is less than one year. Only half the women with early stage endometrial cancer and poor prognostic factors such as high grade or deep myometrial invasion will survive for 5 years. Over the past decade, incredible strides have been taken in evaluating systemic therapy for this disease. However, survival rates remain poor. A literature search was conducted using CANCERLIT, EMBASE, Medline, Investigational Drug database (Current Drug Ltd.) and R&D Focus (IMSworld Publications). The references of the articles were also explored. Search terms included: endometrial cancer, chemotherapy, endocrine/hormonal therapies, molecular biologics, and specific drug names. Progestin therapy offers a 10-20% response rate and survival of less than 1 year. Progestins are most effective in women with well-differentiated tumours and a long disease-free interval. There is no role for adjuvant progestin therapy in early stage disease. Single-agent chemotherapy with the most activity includes ifosfamide, cisplatin/carboplatin, doxorubicin and paclitaxel. Combination chemotherapy provides a response rate of 40-60%; however, median survival is still less than a year. New areas of research include the identification and evaluation of new active endocrine therapies (i.e. LY353381.HCl and letrozole), chemotherapeutics (i.e. herceptin), evaluating chemotherapeutic agents in combination (i.e. paclitaxel, doxorubicin and platinum), in addition to radiation or instead of radiation. New avenues under development involve the specific molecules and pathways responsible for the initiation and growth of endometrial carcinoma, including: tumour suppressor genes, DNA mismatch repair genes, oncogenes, molecules involved in adhesion and invasion and angiogenesis. Further significant advances in radiotherapy, hormonal therapy and chemotherapy are unlikely. Exciting developments in understanding the molecules involved in tumour development and metastasis will allow the development of specific and selective inhibitors.
UI - 11801880
AU - Naumann RW
TI - The role of radiation therapy in early endometrial cancer.
SO - Curr Opin Obstet Gynecol 2002 Feb;14(1):75-9
AD - Division of Gynecologic Oncology, The Blumenthal Cancer Center at Carolinas Medical Center, Charlotte, North Carolina 28211, USA. email@example.com
Few randomized studies have addressed the best choice of adjuvant radiation therapy after surgery for stage I endometrial cancer. Although whole pelvic radiation decreases the incidence of pelvic and vaginal cancer recurrence, there is no convincing evidence that it improves survival in women who have been completely staged. Several studies have indicated that women with high-risk stage I endometrial adenocarcinoma are treated adequately with extended surgical staging and vaginal cuff radiation. In the absence of randomized trials suggesting that whole pelvic radiation improves survival, it should be limited only to the highest risk stage I subgroups. Vaginal cuff brachytherapy appears to provide excellent local control of disease with minimal morbidity.
UI - 11891178
AU - Zysman MA; Chapman WB; Bapat B
TI - Considerations when analyzing the methylation status of PTEN tumor suppressor gene.
SO - Am J Pathol 2002 Mar;160(3):795-800
AD - Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Epigenetic mechanisms of gene silencing, including promoter hypermethylation of tumor suppressor genes, have been shown to contribute to tumorigenesis. PTEN is an important tumor suppressor implicated in the pathogenesis of a number of familial and sporadic cancers. Germline mutations of PTEN predispose to dominantly inherited hamartomatous disorders Cowden syndrome and Bannayan-Zonana syndrome. Somatic PTEN mutations commonly occur in endometrial, breast, prostate, and thyroid tumors. Several investigators have speculated on PTEN promoter hypermethylation as a possible mechanism of PTEN inactivation but data supporting such observations is not forthcoming. The genomic sequence of PTEN is 98% identical to a highly conserved processed PTEN pseudogene (psiPTEN) and this sequence identity extends 841 base pairs into the promoter region. This high degree of homology has made analysis of the methylation status of the PTEN promoter quite challenging. We have investigated the methylation profiles of the promoter region of PTEN in endometrial, breast, and colon cancer cell lines, as well as in a panel of primary endometrial tumors using a combination of methylation-specific polymerase chain reaction, methylation-sensitive restriction analysis, and bisulfite sequencing. Our results show that the pseudogene, and not PTEN, is predominantly methylated in cell lines and tumors. Without careful consideration of the critical nucleotide differences between the two sequences, results obtained from PTEN analysis may not necessarily represent the methylation status of PTEN.
UI - 11868242
AU - Basta A; Pitynski K; Oplawski M; Peszek W; Przeszlakowski D; Basta P
TI - [Pathological parameters of endometrial cancer and presence of metastases in pelvic lymph nodes]
SO - Przegl Lek 2001;58(9):836-8
AD - Katedra Ginekologii i Onkologii CM UJ 31-501 Krakow, ul. Kopernika 23. firstname.lastname@example.org
Endometrial cancer has become a more frequent neoplasm of the female genital tract. The role of lymphadenectomy in surgical treatment of this neoplasm has not been finally defined. The aim of the study was to determine relationship between pathological parameters of endometrial cancer and presence of metastases in pelvic lymph nodes. Forty one patients with endometrial cancer were treated by extended hysterectomy with pelvic lymphadenectomy. The precise Fisher test and logistic regression test were applied in the analysis of relationship. An intrinsic connection between presence of metastases in pelvic lymph nodes and cancer grade, depth of myometrium infiltration depth and infiltration of vascular spaces was found. On the other hand, histological type of neoplasm and characteristic of its growth does not seem to have connection with presence of metastases in pelvic lymph nodes. Pelvic lymphadenectomy seems to give profound information of of process advancement and indications for supplementary treatment.
UI - 11888854
AU - Morice P; Camatte S; Fondrinier E; Rodier JF; Pomel C; Haie-Meder C;
TI - Pautier P; Lhomme C; Duvillard P; Castaigne D [What hysterectomy procedure should be carried out for cancer of the endometrium in stage I-II]
SO - Bull Cancer 2002 Feb;89(2):157-9
AD - Institut Gustave-Roussy, 94805 Villejuif Cedex, France.
UI - 11917573
AU - Nakagawa-Okamura C; Sato S; Tsuji I; Kuramoto H; Tsubono Y; Aoki D; Jobo
TI - T; Oomura M; Hisamichi S; Yajima A Effectiveness of mass screening for endometrial cancer.
SO - Acta Cytol 2002 Mar-Apr;46(2):277-83
AD - Departments of Obstetrics and Gynecology and of Public Health, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. email@example.com
OBJECTIVE: To investigate the effectiveness of mass screening for endometrial cancer using Endocyte (Laboratoire CCD, Paris, France) endometrial smears. STUDY DESIGN: The study subjects were consecutive patients with documented endometrial cancer diagnosed between January 1, 1989, and December 31, 1997, at 22 hospitals in Japan. One hundred twenty-six cases were detected by mass screening and 1,069 diagnosed in outpatient clinics. We compared the stage of cancer at diagnosis and survival rate of patients in the two groups. RESULTS: Early stage was significantly more frequent in the screening group (P < .001); stage I comprised 88.1% of the screening group as compared with 65.3% of the outpatient group. Well-differentiated adenocarcinoma was significantly more frequent in the screening group (P < .01); grade 1 constituted 74.7% of the screening group as compared with 61.0% of the outpatient group. The five-year survival rate was significantly higher in the screening group than in the outpatient group (94.0% vs. 84.3%, P = .041). The crude hazard ratio (HR) of dying of endometrial cancer for the screening group as compared to the outpatient group was .47 (95% CI .22-.99, P = .048). HR became .96 (95% CI .45-2.08, P = .925) after adjustment for age, study area and cancer stage. CONCLUSION: The results suggest that an endometrial cancer screening program would lead to early detection and improved survival among women with endometrial cancer.
UI - 11917574
AU - Morimura Y; Nishiyama H; Hashimoto T; Takano Y; Yamada H; Yanagida K;
TI - Sato A Diagnosing endometrial carcinoma with cervical involvement by cervical cytology.
SO - Acta Cytol 2002 Mar-Apr;46(2):284-90
AD - Department of Obstetrics and Gynecology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
OBJECTIVE: To assess the relationship of a cervical cytologic diagnosis based on number, size and degeneration of malignant clusters and necrotic background to cervical involvement of endometrial carcinoma. STUDY DESIGN: Cervical smears of 53 women with endometrial carcinoma were evaluated for cervical involvement. The cytologic diagnosis was compared with actual involvement, and accuracy was calculated. Retrospectively, cytologic features, including number, size and degeneration of malignant clusters and necrotic background, were analyzed in involved and noninvolved cases. RESULTS: Cervical involvement was confirmed in 15 patients (28.3%). The number and size of malignant clusters in the involved cases were significantly larger than those in the noninvolved cases (P < .001 and < .01, respectively). The proportion of degenerated malignant cells and necrotic background in involved cases were significantly higher than those in noninvolved cases (P < .05). Cytologic diagnosis had a sensitivity and specificity of 62.5% and 86.8%, respectively. CONCLUSION: Cervical smears of involved cases revealed a large number and large size of malignant clusters. These findings support cytologic diagnosis based on number, size and degeneration of malignant cells and necrotic background. Cervical cytology is useful to exclude cervical involvement because of its high specificity and can help detect cervical involvement because of its moderately high sensitivity.
UI - 11917578
AU - Heber E; Schwint AE; Sartor B; Nishihama S; Sanchez O; Brosto M; Itoiz
TI - ME AgNORs as an early marker of sensitivity to radiotherapy in gynecologic cancer.
SO - Acta Cytol 2002 Mar-Apr;46(2):311-6
AD - Department of Radiobiology, National Atomic Energy Commission, Avenida del Libertador 8250 (1429), Buenos Aires, Argentina.
OBJECTIVE: To evaluate the changes induced in silver-stained nucleolar organizer regions (AgNORs) by the first fraction of a radiotherapy protocol for gynecologic cancer on exfoliated cytologic samples to predict the therapeutic success of the full protocol. STUDY DESIGN: Thirteen gynecologic cancer patients who were scheduled for radiotherapy were included in the study. Cell smears were taken from the affected area before and after the first fraction of a radiotherapy protocol and silver stained for AgNORs. AgNORs per nucleus were counted under a light microscope. Local disease control by the full radiotherapy protocol was assessed at one year by the Papanicolaou technique. RESULTS: Local success of radiotherapy was greater for lesions with higher pretreatment AgNOR counts and for lesions that underwent a greater percentage reduction in AgNOR counts after the first fraction. We correlated local success of the full radiotherapy protocol with a predictive index based on AgNOR counts obtained before and after the first fraction. CONCLUSION: A predictive index based on AgNOR counts can predict, as early as after the first fraction, the local control of disease by a full radiotherapy protocol. Knowledge of the probability of success long before the protocol is completed would allow reevaluation of therapeutic options.
UI - 11889221
AU - Grundker C; Gunthert AR; Millar RP; Emons G
TI - Expression of gonadotropin-releasing hormone II (GnRH-II) receptor in human endometrial and ovarian cancer cells and effects of GnRH-II on tumor cell proliferation.
SO - J Clin Endocrinol Metab 2002 Mar;87(3):1427-30
AD - Department of Gynecology and Obstetrics, Georg-August-University, D-37070 Gottingen, Germany.
Recently it was shown that a second GnRH system exists in primates. This study was conducted to investigate whether or not the receptor specific for GnRH type II is expressed in human endometrial and ovarian cancer cells and whether or not GnRH-II has effects on tumor cell proliferation. Expression of GnRH-II receptor mRNA in endometrial and ovarian cancer cell lines was demonstrated using RT-PCR and Southern blot analysis. The proliferation of these cell lines was dose- and time-dependently reduced by native GnRH-II. These effects were significantly more potent than the anitproliferative effects of equimolar doses of GnRH-I agonist Triptorelin (p<0.001). In the GnRH-II receptor positive but GnRH-I receptor negative ovarian cancer cell line SK-OV-3 native GnRH-II but not GnRH-I agonist Triptorelin had antiproliferative effects.
UI - 11818111
AU - Bakour SH; Gupta JK; Khan KS
TI - Risk factors associated with endometrial polyps in abnormal uterine bleeding.
SO - Int J Gynaecol Obstet 2002 Feb;76(2):165-8
AD - Birmingham Minimal Access Surgical Training (MAST) Centre, Academic Department of Obstetrics and Gynaecology, University of Birmingham, Birmingham, UK.
OBJECTIVES: To evaluate the significance of various risk factors associated with endometrial polyps in women with abnormal uterine bleeding. METHODS: A prospective cohort study of 248 consecutive patients evaluated for abnormal uterine bleeding in a Rapid Access Ambulatory Diagnostic (RAAD) clinic was carried out from 1996 to 1997. Endometrial polyps were diagnosed using outpatient hysteroscopy and their histological nature was confirmed in all patients by performing inpatient polypectomy. Multivariate logistic regression modeling was used to evaluate the effects of age, parity, menopausal status, hormone replacement therapy and tamoxifen treatment on the occurrence of polyps. RESULTS: In an analysis adjusted for the effects of age, parity and menopausal status, tamoxifen treatment was associated with endometrial polyps (adjusted odds ratio 11.21, 95% confidence interval 2.70-46.46, P=0.0009) but hormone replacement therapy was not (adjusted odds ratio 1.48, 95% confidence interval 0.68-3.20, P=0.32). CONCLUSION: Our study confirmed that tamoxifen is associated with endometrial polyps. However, it rejects the hypothesis that hormone replacement therapy is a risk factor for endometrial polyps.
UI - 11920532
AU - Dove-Edwin I; Boks D; Goff S; Kenter GG; Carpenter R; Vasen HF; Thomas
TI - HJ The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma.
SO - Cancer 2002 Mar 15;94(6):1708-12
AD - Imperial Cancer Research Fund Family Cancer Clinic, St Mark's Hospital, London, UK.
BACKGROUND: Endometrial carcinoma is the most common extracolonic malignancy associated with hereditary nonpolyposis colorectal carcinoma syndrome (HNPCC). The risk of endometrial carcinoma in HNPCC mutation carriers is approximately ten times that of the general population, and endometrial ultrasound surveillance to detect early cancer in asymptomatic individuals is recommended by the International Collaborative Group on HNPCC. There is little, if any, published data addressing the effectiveness of surveillance in HNPCC and familial colorectal carcinoma. METHODS: The outcomes of endometrial carcinoma surveillance scans were collected from the St Mark's Hospital Imperial Cancer Research Fund Family Cancer Clinic in the UK and the Netherlands Foundation for the Detection of Hereditary Tumors. Two hundred ninety two women from HNPCC (171) or HNPCC-like (98) families between the ages of 25-65 years were offered pelvic ultrasound surveillance scans for a period of up to 13 years. RESULTS: Results were available from 269 women. The study period included a total of 825.7 years of risk. Two cases of endometrial carcinoma were reported. Neither case was detected by surveillance scanning. Both cases presented at an early stage with symptoms and were subsequently cured. CONCLUSIONS: Endometrial carcinoma surveillance in hereditary colorectal carcinoma may not offer obvious clinical benefits. Copyright 2002 American Cancer Society.
UI - 11920503
AU - Di Nezza LA; Misajon A; Zhang J; Jobling T; Quinn MA; Ostor AG; Nie G;
TI - Lopata A; Salamonsen LA Presence of active gelatinases in endometrial carcinoma and correlation of matrix metalloproteinase expression with increasing tumor grade and invasion.
SO - Cancer 2002 Mar 1;94(5):1466-75
AD - Prince Henry's Institute of Medical Research, Clayton, VIC, Australia. Lisa.Di.Nezza@med.monash.edu.au
BACKGROUND: The actions of the extracellular-matrix degrading enzymes, matrix metalloproteinases (MMPs), are implicated in tumorigenesis. The cellular localization of MMP-2, MMP-9, membrane type 1 (MT1)-MMP, tissue inhibitors of metalloproteinases (TIMPs) 1-3, and the presence of active gelatinases were investigated in endometrial carcinoma. METHODS: Endometrial carcinomas were grouped according to histologic grade (Grades 1-3), depth of myometrial invasion (0, < 50%, > 50%) and the presence of vascular/lymphatic invasion. Twenty-nine endometrial carcinoma biopsies were investigated immunohistochemically to determine the tissue localization of MMP-2 (gelatinase A), MMP-9 (gelatinase B), MT1-MMP, and TIMPs 1-3. In situ hybridization was performed to localize MMP-2 and MMP-9 mRNA. The presence of active gelatinases was assessed using in situ zymography. RESULTS: Epithelial tumor cells were the main site of MMP-2, MMP-9, and MT1-MMP protein. Variable stromal cell localization was also observed, particularly in areas adjacent to tumor nests. Semiquantitative analysis revealed increases in MMP-9 and MMP-2 but not MT1-MMP staining scores in tumor epithelial cells in the transition from histologic Grade 1 to Grades 2 and 3. Matrix metalloproteinase-9 and MT1-MMP staining scores in tumor cells were significantly associated with the presence of myometrial invasion and vascular/lymphatic invasion, while MMP-2 did not correlate with these factors. In addition, MT1-MMP was co-localized with MMP-2, supporting its role in the activation of proMMP-2. Tumor cells from all histologic grades stained intensely for TIMP-2 and TIMP-3 proteins, while variable stromal staining was observed. In Grade 1 carcinomas TIMP-1 was predominantly immunolocalized to the stromal compartment with variable tumor cell localization being observed in Grades 2 and 3 carcinomas. Matrix metalloproteinase-9 and MMP-2 mRNAs were predominantly observed in tumor epithelial cells as well as in the stroma to varying degrees. In situ zymography revealed active forms of gelatinases at the cellular surface and in association with tumor epithelial cells within endometrial carcinoma tissues. CONCLUSIONS: These data suggest that increasing expression of MMPs and endometrial carcinoma progression are closely related. Active gelatinases are present in endometrial carcinoma, resulting in alterations to the microenvironment that promote tumor invasion and metastasis. Copyright 2002 American Cancer Society.
UI - 11801550
AU - Stefansson I; Akslen LA; MacDonald N; Ryan A; Das S; Jacobs IJ; Salvesen
TI - HB Loss of hMSH2 and hMSH6 expression is frequent in sporadic endometrial carcinomas with microsatellite instability: a population-based study.
SO - Clin Cancer Res 2002 Jan;8(1):138-43
AD - Department of Pathology, The Gade Institute, Bergen, Norway.
Microsatellite instability (MSI) seems to be important in the development of various human cancers including sporadic endometrial cancer. It has previously been shown that alterations in the mismatch repair gene hMLH1 seem to be important for the development of MSI in these tumors. The role of the other mismatch repair genes hMSH2 and hMSH6 has been less well studied, but investigations on patients with hereditary nonpolyposis colorectal cancer indicate that these genes also may be involved. We therefore wanted to investigate the pattern of hMSH2 and hMSH6 expression in a prospective and population-based series of endometrial carcinomas with known hMLH1 expression and MSI status. A total of 138 patients were studied, and pathological staining was seen in 19 cases (14%) for hMLH1, 26 cases (19%) for hMSH2, and 17 cases (12.3%) for hMSH6. Pathological hMLH1 expression was more frequent among tumors with high MSI (those positive for four to five of five markers), whereas pathological expression of hMSH2 and hMSH6 was more frequent among tumors with intermediate MSI (those positive for two to three of five markers). MSI was significantly correlated with pathological expression of hMLH1 (P < 0.001), hMSH2 (P = 0.04), and hMSH6 (P = 0.001). In the group with high MSI, 14 of 16 tumors (88%) showed pathological expression for at least one of the markers. The expression of hMLH1, hMSH2, or hMSH6 did not significantly influence survival. In conclusion, pathological expression of hMLH1 does not seem to account for all tumors with a MSI-positive phenotype in this population-based series of endometrial carcinomas. Our data indicate that the other mismatch repair genes hMSH2 and hMSH6 are also involved, especially in cases with intermediate MSI.
UI - 11915181
AU - Hadaczek P; Gronwald J; Chosia M; Huebner K; Lubinski J
TI - Fhit protein expression in endometrial cancers: no correlation with histological grade.
SO - Pol J Pathol 2001;52(4):199-203
AD - Department of Genetics and Pathology, Pomeranian Academy of Medicine, Szczecin. firstname.lastname@example.org
The genes specifically involved in endometrial cancers have not yet been discovered. The FHIT gene, a tumour suppressor located at 3p14.2, is altered in many human tumours, including those derived from the female genital tract. We have thus investigated the status of Fhit protein expression in endometrial carcinomas (EC), and its association with histological grade of malignancy in order to determine if Fhit expression is inactivated in EC and if so, whether it is inactivated during initiation or progression. Recent studies have reported that alteration in the FHIT locus detected by DNA and RNA analysis is well correlated with loss of Fhit protein expression in tumours. Thus, we characterised Fhit protein expression as an indication of FHIT gene status in 35 cases of EC of different histological grade (G1: 13 cases; G2: 14 cases; G3: 8 cases). In our group of cancers, Fhit protein expression was absent or reduced in 37% (13/35) of EC. The first 13 cases, judged as G1, showed Fhit deficiency in approximately 38.5% of cases (5/13). For G2 and G3 tumours these numbers were similar and accounted for approximately 35.7% (5/14) and approximately 37.5% (3/8), respectively. No statistical difference was found for Fhit expression among the various groups of tumours, which allowed us to conclude that morphological grade does not seem to be an important factor. Our results suggest that Fhit inactivation is an early event in carcinogenesis of the endometrium. As this observation is contrary to some already published reports, another independent study with larger amounts of material is necessary to determine this issue definitely.
UI - 11898145
AU - Mahon SM; Williams MT; Spies MA
TI - Screening for second cancers and osteoporosis in long-term survivors.
SO - Cancer Pract 2000 Nov-Dec;8(6):282-90
AD - Saint Louis University, Division of Hematology/Oncology, P.O. Box 15250, St. Louis, MO 63110-0250, USA.
PURPOSE: The purpose of this preliminary study was to describe the extent to which healthcare providers recommend the screening strategies for early detection described by the American Cancer Society (ACS), for breast, gynecologic, and colorectal cancer, and by the National Osteoporosis Foundation (NOF), for osteoporosis, to women who are long-term survivors of breast, ovarian, or endometrial cancer. DESCRIPTION OF THE STUDY: A four-part survey was developed for this study, with the first three parts based on the ACS guidelines for breast, gynecologic, and colorectal cancer screening and the NOF guidelines for osteoporosis screening. The fourth part related to personal characteristics, setting, knowledge, and perceptions of the nurses surveyed. A random sample of outpatient nurses was obtained from the Oncology Nursing Society. Of 668 nurses, 321 (48%) responded (Oncology Certified Nurse (OCN) 68.1%; Advanced Oncology Certified Nurse (AOCN) 16.6%). RESULTS: The most consistently performed screenings that were reported were mammogram (range 74.2-87.7%), professional breast examination (range 73.9-83.7%), and Pap test and pelvic examination (range 61.8-85.2%). The least frequently performed screenings are flexible sigmoidoscopy/colonoscopy (range 20.2-27.7%), bone mineral density testing (range 16.9-19.0%), and height measurement (range 22.5-28.3%). Less than one third of survivors are offered counseling on strategies to promote bone health. CLINICAL IMPLICATIONS: Knowledge of factors associated with osteoporosis and the use of screening strategies for second malignancies in survivors of breast, ovarian, and endometrial cancers can be used to implement activities such as patient education and clinical practice protocols that will increase the use of current screening recommendations.
UI - 11797159
AU - Steiner E; Eicher O; Hofmann M; Weikel W; Schmidt M; Pilch H; Knapstein
TI - PG [Endometrial carcinoma in patients with diabetes mellitus]
SO - Zentralbl Gynakol 2001 Nov;123(11):622-5
AD - Universitats-Frauenklinik, Johannes Gutenberg-Universitat Mainz. email@example.com
OBJECTIVE: The purposes of this study were to analyze the relationship between clinical and pathological risk factors in endometrial cancer and additional diabetes mellitus and to clarify the correlation between additional diabetes mellitus and survival of patients with this disease. - MATERIAL AND METHODS: This analyze included 181 patients with endometrial carcinoma who were treated between 1985 and 1995 at the University hospital Mainz. Patients with sarcoma were excluded. For statistical analysis a chi(2)-test was performed for univariat analysis. A Kaplan-Meier procedure was performed for over all survival and disease free interval and COX-Regression for multivariate analysis of independence. - RESULTS: The mean follow-up period was 49 months. The mean age was 65 years. 21.8 % of the patients had an additional diabetes mellitus. These patients had a significantly deeper infiltration of the Myometrium (p-value = 0.004) and were more likely to have lymphonode metastasis (p-value = 0.02). - CONCLUSION: Our results show a correlation between Diabetes mellitus and adverse prognostic factors witch affects by the rate of lymphonode spread and overall survival.
UI - 11920468
AU - Hamid AA; Mandai M; Konishi I; Nanbu K; Tsuruta Y; Kusakari T; Kariya M;
TI - Kita M; Fujii S Cyclical change of hMSH2 protein expression in normal endometrium during the menstrual cycle and its overexpression in endometrial hyperplasia and sporadic endometrial carcinoma.
SO - Cancer 2002 Feb 15;94(4):997-1005
AD - Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Kyoto, Japan.
BACKGROUND: The role of hMSH2 protein, one of the major DNA repair proteins, until now, had not been elucidated in terms of normal endometrial function during the menstrual cycle. The current study was designed to address this issue and to determine whether the expression of hMSH2 is altered in the course of endometrial carcinogenesis. METHODS: Immunohistochemical reactivity with a monoclonal antibody against the hMSH2 protein was examined in endometrial tissue specimens from 45 patients with normal endometrium, 51 patients with endometrial hyperplasia, and 27 patients with endometrial carcinoma. Immunohistochemical expression of proliferating cell nuclear antigen (PCNA) also was studied in the same samples as a measure of the proliferative activity and was compared with hMSH2 expression in each sample. RESULTS: The functional layer of normal endometrium displayed cyclic changes in hMSH2 protein expression during the menstrual cycle, showing positive expression in the proliferative phase and becoming weak to negative in the secretory phase. This expression pattern was similar to that of PCNA. Sixty-three percent of endometrial carcinomas showed strong positivity for both hMSH2 and PCNA expression, and 7.4% had an intensity of hMSH2 protein expression similar to that found in normal proliferative endometrial glandular cells. There was only 1 sample (3.7%) that was completely negative for hMSH2 expression, and 26% of samples were weakly positive for PCNA and hMSH2 protein. All simple hyperplasias and the majority of complex and atypical hyperplasias showed positive immunoreactivity for hMSH2 and PCNA. CONCLUSIONS: This study demonstrates that hMSH2 protein expression changes during the menstrual cycle in parallel with proliferative activity. In most patients with sporadic endometrial carcinoma, the expression of hMSH2 protein is consistent with PCNA expression. In contrast, loss of hMSH2 expression is observed rarely in patients with sporadic endometrial carcinoma. Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10341
UI - 11821605
AU - Vilos GA; Harding PG; Silcox JA; Sugimoto AK; Carey M; Ettler HC
TI - Endometrial adenocarcinoma encountered at the time of hysteroscopic endometrial ablation.
SO - J Am Assoc Gynecol Lapa