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Abramson Cancer CenterNCI CANCERLIT® Search: Thyroid Cancer - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
UI - 11405089
AU - Dotzenrath C; Goretzki PE; Cupisti K; Simon D; Witte J; Yang Q; Ohmann
TI -
C; Roher HD
Is there any consensus in diagnostic and operative strategy with respect
to medullary thyroid cancer? A questionnaire answered by 73 endocrine
surgical units.
SO - Langenbecks Arch Surg 2001 Feb;386(1):47-52
AD - St. Antonius Kliniken, Marienheim, Hardtstr. 46, D-42107 Wuppertal,
Germany. Dotzenr@uni-duesseldorf.de
BACKGROUND: The purpose of this investigation was to analyze the
individual diagnostic and operative strategy in the treatment of
medullary thyroid carcinoma (MTC) in international specialized centers
and to assess whether standard procedures are carried out in practice
everywhere. METHODS: A questionnaire concerning diagnosis and treatment
of patients with primary, persistent, or recurrent sporadic or familial
MTC was sent to 263 members of the International Association of
Endocrine Surgeons. RESULTS: Primary treatment of MTC does not show
significant differences for patients with sporadic or familial disease
(Chi-square, n.s.), and standard procedures are performed in only 25-40%
of patients. Computed tomography scan is the most common localization
procedure in persistent or recurrent disease (52-72%), followed by
scintigraphy (43-71%), ultrasonography (41-56%), and magnetic resonance
imaging (31-49%). In case of negative localization studies, 68-86% of
colleagues do not recommend reoperation. In symptomatic patients with
stage-IV tumors, however, 84% of colleagues advocate reoperation to
provide relief from the tumor burden. CONCLUSIONS: Even with experienced
endocrine surgeons, a consensus to uni- and/or bilateral neck dissection
in primary MTC is lacking. The majority of authors supports at least
total thyroidectomy with central lymph-node dissection. In recurrent
disease, there is a general tendency to reoperate in case of positive
localization studies and in case of symptomatic disease.
2
UI - 11454041
AU - Mai KT; Landry DC; Thomas J; Burns BF; Commons AS; Yazdi HM; Odell PF
TI -
Follicular adenoma with papillary architecture: a lesion mimicking
papillary thyroid carcinoma.
SO - Histopathology 2001 Jul;39(1):25-32
AD - Division of Anatomical Pathology, Department of Laboratory Medicine, The
Ottawa Hospital, Ontario, Canada. ktmai@civich.ottawa.on.ca
AIMS: The purpose of this study was to investigate the significance of
'benign' encapsulated follicular thyroid nodules with papillary
structures. METHODS AND RESULTS: Twenty-one cases of encapsulated
neoplastic thyroid nodules with papillary structures and nuclear
features not diagnostic of papillary thyroid carcinoma (PTC) were
obtained. All cases were reviewed with particular attention to nuclear
features (fine chromatin pattern, optical clearing, grooves and
inclusions). Representative sections were submitted for measurement of
the maximum diameter of 200 round or nearly round nuclei and for
immunostaining for MIB1, CK19, HBME and Ret oncogene protein. Nine cases
displayed scattered optically clear nuclei or nuclear grooves in less
than 30% of total neoplastic cells. They were grouped in the category of
thyroid nodules with limited nuclear features of papillary thyroid
carcinoma (PTC), but not diagnostic of PTC. The other 12 cases had fine
or coarse chromatin, but lacked other features of nuclei in PTC. The
diameter of the nuclei ranged from 5.6 to 7.2 microm and were smaller
than those of PTC (6.3-10.0 microm). Immunostaining revealed positive
reactivity for MIB1 in the papillary structures. Immunostaining for CK19
and HBME varied from negative or focally weak to diffusely moderate
reactivity. Ret oncogene protein immunostaining showed focal and weak
reactivity in one case and was negative in other cases of the study.
Clinical follow-up from 6 months to 15 years revealed no evidence of
metastasis. CONCLUSIONS: The papillary structures in the study cases are
unlikely to represent degenerative changes due to their proliferative
activity. In view of (i) the encapsulation and the uniformity of the
constituent cells, (ii) the varying degrees of immunoreactivity for CK19
and HBME and negative immunoreactivity for Ret oncogene protein, and
(iii) the absence or insufficiency of nuclear criteria for the diagnosis
of PTC and the absence of lymph node metastasis in all study cases, we
believe that these lesions represent the papillary variant of follicular
adenoma. Recognition of this pathological entity is important to avoid
an over-diagnosis of PTC.
3
UI - 11737313
AU - Stephenson TJ
TI -
Papillary carcinoma of the thyroid: a tumour still with no benign
neoplastic counterpart.
SO - Histopathology 2001 Nov;39(5):536-8
AD - Department of Histopathology, Sheffield Teaching Hospitals, Sheffield,
UK. tim.stephenson@sth.nhs.uk
4
UI - 11484280
AU - Velkov M; Mendizov I; Dashev G
TI -
[Recurrent nodular goiter. Characteristic features and surgical
management]
SO - Khirurgiia (Sofiia) 2000;56(2):17-9
Purpose of the study was to investigate the frequency of the thyroid
carcinoma in the recurrent nodular goiter, to analyse the applied
operative methods, the observed complications and the obtained early and
distant postoperative results. For the period 1985-1996 in the Clinic of
Endocrine Surgery were performed 588 reoperations by 577 patients with
nodular recurrent goiter, distributed as following: 539 females, aged
14-81 and 49 males, aged 11-69. In 431 cases (73%) was applied medial
approach and in 157 cases (27%)--lateral operative approach by the
mobilizing of the thyroid recurrence. In the early postoperative period
were established the following complications: clinical
hypoparathyroidism in 10 patients (1.7%) with calcium level from
1.44-2.01 mmol/l and recurrent nerve paralysis in 28 patients (4.76%),
including: in 13 cases unilateral paralysis on the right side, in 9
cases unilateral--on the left side and in 6 cases--bilateral paralysis.
The established in 28 patients (4.76%) thyroid carcinoma and the
appeared in 59 cases (10%) new recurrence of the basic thyroid disease
supported our tactic for radical operative treatment in all patients
with nodular recurrent goiter.
5
UI - 11783847
AU - Radivoyevitch T; Sachs RK; Nikiforov YE; Nikiforova MN; Little MP
TI -
On target cell numbers in radiation-induced H4-RET mediated papillary
thyroid cancer.
SO - Radiat Environ Biophys 2001 Sep;40(3):191-7
AD - Department of Epidemiology and Biostatistics, Case Western Reserve
University, Cleveland, OH 44106, USA. radivot@hal.cwru.edu
Radiation-induced human papillary thyroid cancer (PTC) is associated
with chromosomal inversions that involve the genetic loci H4 and RET on
chromosome 10. Recently, experimental data has shown that these loci lie
in very close spatial proximity in a high proportion of adult human
thyroid cells. Applying the generalized formulation of dual radiation
action to this H4-to-RET geometric distance data, we predict here the
radiation dose-response of H4-RET induction. The predicted H4-RET
dose-response has a linear-to-quadratic transition dose of approximately
7 Gy, suggesting the validity of linear risk extrapolations to very low
doses for H4-RET mediated radiation-induced PTC. In conjunction with
A-bomb survivor data, the predicted H4-RET dose-response yields
estimates of the number of PTC target cells that are of the order of
approximately 10(6) to approximately 10(7) cells, i.e. considerably less
than the total number of follicular cells in the thyroid gland.
6
UI - 11900218
AU - Sanso GE; Domene HM; Garcia R; Pusiol E; de M; Roque M; Ring A;
TI -
Perinetti H; Elsner B; Iorcansky S; Barontini M
Very early detection of RET proto-oncogene mutation is crucial for
preventive thyroidectomy in multiple endocrine neoplasia type 2
children: presence of C-cell malignant disease in asymptomatic carriers.
SO - Cancer 2002 Jan 15;94(2):323-30
AD - Centro de Investgaciones Endocrinologicas, Hospital de Ninos R.
Gutierrez, Buenos Aires, Argentina.
BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) is an inherited
disease caused by germline mutations in the RET proto-oncogene, and is
responsible for the development of endocrine neoplasia. Its prognosis is
dependent on the appearance and spread of medullary thyroid carcinoma
(MTC). Relatives at risk can be identified before clinical or
biochemical signs of the disease become evident. METHODS: Twenty-one
families with MEN 2 (16 families with MEN 2A and 5 families with MEN 2B)
were studied. Peripheral blood DNA was amplified by polymerase chain
reaction. DNA sequence or restriction enzyme analysis was performed to
detect mutations of RET proto-oncogene exons 10, 11, and 16. Molecular
analysis was carried out in all index patients as well as in 98
relatives of MEN 2A patients (60 juveniles, ages 6 months to 21 years,
and 38 adults, ages 22 to 81 years) and in 13 relatives (6 juveniles
ages 10 to 21 years, and 7 adults ages 41 to 66 years) from MEN 2B
families. RESULTS: Molecular studies showed a mutation at codon 634,
exon 11 in all MEN 2A patients. All MEN 2B patients showed an ATG to ACG
(Met918Thr) mutation. In MEN 2A families, 42 out of 98 relatives were
affected. Total thyroidectomy was performed in 18 juvenile carriers ages
17 months to 21 years. Histopathologic studies of the glands revealed
parafollicular cell (C-cell) hyperplasia in all of these carriers,
medullary thyroid carcinoma in 15 carriers, and only one carrier with
lymph node metastases. CONCLUSIONS: The consistent finding of C-cell
disease in all the juvenile carriers who underwent preventive
thyroidectomy emphasizes the relevance of early screening in children at
risk of developing MTC. The presence of MTC in the specimen of
prophylactic thyroidectomy from a 17 month old girl highlights the
importance of thyroidectomy as soon as the molecular diagnosis is
confirmed.
7
UI - 11917600
AU - Us-Krasovec M; Flezar M; Kloboves-Prevodnik V
TI -
Rare cytologic findings in medullary thyroid carcinoma.
SO - Acta Cytol 2002 Mar-Apr;46(2):434-6
8
UI - 11886336
AU - Belchetz G; Cheung CC; Freeman J; Rosen IB; Witterick IJ; Asa SL
TI -
Hurthle cell tumors: using molecular techniques to define a novel
classification system.
SO - Arch Otolaryngol Head Neck Surg 2002 Mar;128(3):237-40
AD - Department of Otolaryngology, Mount Sinai Hospital, 600 University Ave,
Suite 401, Toronto, Ontario, Canada M5G 1X5.
BACKGROUND: Since ret/PTC gene rearrangements are specific to papillary
thyroid carcinoma (PTC), the diagnosis of Hurthle cell PTC (HCPTC) has
recently been expanded to include a subset of Hurthle cell tumors (HCTs)
that may lack both papillary architecture and/or classic nuclear
features but that harbor a ret/PTC gene rearrangement. We hypothesize
that such HCPTCs behave in a fashion analogous to other papillary
carcinomas, while Hurthle cell carcinomas (HCCs) behave similarly to
follicular carcinomas. EDUCATIONAL OBJECTIVES: At the conclusion of this
article, participants should be able to discuss HCTs and to identify
HCPTCS using molecular techniques. METHODS: A retrospective chart review
was carried out on 56 patients with HCTs. All pathological specimens
were analyzed for ret/PTC gene rearrangements. Hurthle cell adenoma
(HCA) was defined as an HCT that did not exhibit capsular and/or
vascular invasion and that lacked a ret/PTC gene rearrangement when
evaluated by immunohistochemical and reverse transcription polymerase
chain reaction analysis. An HCC was defined as an HCT with capsular
and/or vascular invasion that lacked a ret/PTC gene rearrangement, and
an HCPTC was defined as any HCT that harbored a ret/PTC gene
rearrangement. RESULTS: The subclassification of the 56 HCTs was as
follows: 21 HCAs, 15 HCCs, and 20 HCPTCs. No patients with HCA or HCC
were ret/PTC positive. Five of the 6 patients with definite lymph node
metastasis were in the HCPTC group, demonstrating that molecular
analysis helps to explain biological behavior. CONCLUSIONS: Hurthle cell
neoplasms can now be classified using histopathological as well as
molecular criteria. It appears that the new subclassification of
malignant HCTs into follicular (HCC) and papillary (HCPTC) variants
identifies 2 distinct biological groups.
9
UI - 11886339
AU - Khoo ML; Freeman JL; Witterick IJ; Irish JC; Rotstein LE; Gullane PJ;
TI -
Asa SL
Underexpression of p27/Kip in thyroid papillary microcarcinomas with
gross metastatic disease.
SO - Arch Otolaryngol Head Neck Surg 2002 Mar;128(3):253-7
AD - Department of Pathology, University Health Network, 610 University Ave,
Suite 4-302, Toronto, Ontario, Canada M5G 2M9.
OBJECTIVE: Papillary microcarcinomas (PMCs) of the thyroid (measuring
less than 1 cm in maximum dimension) are extremely common incidental
histologic findings, and most of these tumors are not considered
clinically significant. However, rare PMCs behave aggressively and
metastasize early, giving rise to clinically significant metastatic
disease. We hypothesized that p27 and MIB-1/Ki-67 immunoreactivity would
allow us to identify this small subgroup of PMCs that have the potential
to behave aggressively. METHODS: We reviewed the histopathology reports
of 2000 patients who underwent thyroid surgery at our institution
between 1995 and 1999 and identified 22 patients who presented with
gross regional metastases from a primary PMC. The primary and metastatic
tumors were stained for ret, p53, p27, and MIB-1 using the
avidin-biotin-peroxidase complex technique. A control group of 33
nonmetastasizing PMCs was also analyzed. RESULTS: Immunoreactivity for
ret, p53, and MIB-1 showed no difference between metastasizing and
nonmetastasizing PMCs. In most tumors, ret was present, while p53
immunoreactivity was absent in all tumors. MIB-1 staining was present in
a small number of cells in both groups of tumors. Immunoreactivity for
p27 was quantitated by the intensity of expression as well as the
distribution of positive cells within each tumor. All tumors showed
lower p27 expression than normal thyroid tissue. However, metastasizing
PMCs demonstrated a significantly lower expression of p27 than
nonmetastasizing PMCs (P<.001). CONCLUSION: Our results suggest that p27
immunohistochemical analysis may be a valuable diagnostic tool in
predicting aggressive potential in PMCs.
10
UI - 11886341
AU - Roach JC; Heller KS; Dubner S; Sznyter LA
TI -
The value of frozen section examinations in determining the extent of
thyroid surgery in patients with indeterminate fine-needle aspiration
cytology.
SO - Arch Otolaryngol Head Neck Surg 2002 Mar;128(3):263-7
AD - Long Island Surgical Specialists, PC, 410 Lakeville Rd, Suite 310, Lake
Success, NY 11042, USA.
OBJECTIVES: To determine the usefulness of intraoperative frozen section
(FS) examinations in establishing the diagnosis of thyroid cancer in
patients undergoing thyroidectomy for nodules with indeterminate
cytological features and to determine the cost-effectiveness of FS
examinations in this situation. DESIGN: Retrospective medical record
review. The results of fine-needle aspiration biopsies (FNABs), FS
examinations, and final pathologic examinations are compared. A
cost-effectiveness analysis of routine FS examinations compared with the
cost of additional surgical procedures is performed. SETTING: A private
surgical practice in a medical school-affiliated teaching hospital.
PATIENTS: The records of all 480 patients undergoing thyroidectomy
between January 1, 1998, and September 30, 2000, were reviewed. All 199
patients with a dominant thyroid nodule and FNAB results either highly
suggestive of papillary cancer or indeterminate were studied. RESULTS:
Of the patients with FNAB results highly suggestive of papillary cancer,
95% had cancer according to the final pathologic examination results.
The diagnosis of cancer was made by FS examination results in 67% of
these patients. Of the remaining 178 patients whose FNAB result was
indeterminate, 64 (36%) had thyroid cancer. Malignancy was diagnosed by
FS examination results in 30 (47%) of these patients. If FS examinations
had not been performed, these 30 patients would have required a second
operation to complete a total thyroidectomy. The cost savings of routine
FS examinations in patients with indeterminate FNAB results is 1298 US
dollars per patient. CONCLUSIONS: The routine performance of FS
examinations in patients with thyroid nodules with indeterminate
cytological features is a cost-effective way of avoiding a second
surgical procedure if a total thyroidectomy is indicated. In patients
with FNAB results highly suggestive of papillary cancer, FS examinations
are not useful. In these patients, the definitive operation can be based
on the results of the FNAB.
11
UI - 11889153
AU - Kung AW; Chau MT; Lao TT; Tam SC; Low LC
TI -
The effect of pregnancy on thyroid nodule formation.
SO - J Clin Endocrinol Metab 2002 Mar;87(3):1010-4
AD - Department of Medicine, University of Hong Kong, China.
awckung@hkucc.hku.hk
Epidemiology data have revealed a higher prevalence of nodular goiters
in women than men in both iodine-sufficient and iodine-deficient areas.
Increased prevalence of thyroid nodules has also been reported in women
with higher gravidity. However, the association between pregnancy and
thyroid nodule formation has never been studied. The aim of our study
was to evaluate the incidence of thyroid nodules during pregnancy and
determine whether pregnancy will induce thyroid nodule formation. Two
hundred twenty-one healthy southern Chinese women in the first trimester
of their pregnancy were studied prospectively. Thyroid ultrasonography,
thyroid function tests, and urinary iodine excretion were measured at
first, second, and third trimesters of pregnancy as well as 6 wk and 3
months postpartum. Thyroid nodules (>2 mm in any dimension on
ultrasonography) were detected in 34 (15.3%) subjects at first
trimester, with 12 (5.4%) subjects having more than one nodule. Eight
subjects had clinically palpable nodules. Women with thyroid nodules
were older (P < 0.01) and had higher gravidity (P < 0.02) than those
women without thyroid nodules. The volume of the single/dominant nodules
increased from 60 (14--344) mm(3), median (interquartile range) at first
trimester to 65 (26-472) mm(3) at third trimester (P < 0.02). These
nodules remained enlarged at 103 (25-461) mm(3) 6 wk postpartum (P <
0.005) and 73 (22-344) mm(3) at 3 months postpartum (P < 0.05). Patients
with thyroid nodules had lower serum TSH values (P < 0.03) and higher Tg
levels (P < 0.05) throughout pregnancy. Appearance of new nodules was
detected in 25 (11.3%) women as pregnancy advanced so that by 3 months
postpartum, the incidence of thyroid nodular disease was 24.4% (P < 0.02
vs. first trimester). Compared with those with no detectable nodules
throughout pregnancy, subjects with new nodule formation had higher
urinary iodine excretion from second trimester onward (P all < 0.05).
However, no difference could be detected in their TSH and Tg levels
throughout pregnancy. Fine-needle aspiration on nodules greater than 5
mm in any dimension after delivery (n = 21) confirmed the majority
having histological features consistent with nodular hyperplasia. No
thyroid malignancy was detected. In conclusion, pregnancy is associated
with an increase in the size of preexisting thyroid nodules as well as
new thyroid nodule formation. This may predispose to multinodular goiter
in later life.
12
UI - 11889172
AU - Bachleitner-Hofmann T; Stift A; Friedl J; Pfragner R; Radelbauer K;
TI -
Dubsky P; Schuller G; Benko T; Niederle B; Brostjan C; Jakesz R; Gnant M
Stimulation of autologous antitumor T-cell responses against medullary
thyroid carcinoma using tumor lysate-pulsed dendritic cells.
SO - J Clin Endocrinol Metab 2002 Mar;87(3):1098-104
AD - Department of Surgery, University of Vienna Medical School, Vienna,
Austria 1090.
Dendritic cells (DCs) have attracted wide interest because of their
unique capacity to elicit primary and secondary antitumor responses. We
have generated autologous tumor lysate-pulsed DCs from three patients
with medullary thyroid carcinoma (MTC) and tested them for their ability
to stimulate cytotoxic T-cell responses against autologous MTC tumor
cells in vitro. The aim of our investigations was to evaluate the
potential efficacy of DC-based immunotherapy in patients with MTC. DCs
were generated from peripheral blood monocytes using GM-CSF and IL-4
(immature DCs) or GM-CSF, IL-4, and TNFalpha (mature DCs). Our results
indicate that mature tumor lysate-pulsed DCs are able to elicit a human
leukocyte antigen class I-restricted cytotoxic T-cell response against
autologous MTC tumor cells, whereas immature tumor lysate-pulsed DCs do
not stimulate significant antitumor activity. We feel that our data may
be relevant for future clinical trials of active immunotherapy using
tumor lysate-pulsed DCs in patients with MTC who have residual or
distant disease after surgical treatment. The fact that mature DCs
displayed a substantially higher capacity to stimulate autologous
antitumor T-cell responses than immature DCs underlines the importance
of a maturation step in immunotherapy protocols based on DCs.
13
UI - 11889175
AU - Puzianowska-Kuznicka M; Krystyniak A; Madej A; Cheng SY; Nauman J
TI -
Functionally impaired TR mutants are present in thyroid papillary
cancer.
SO - J Clin Endocrinol Metab 2002 Mar;87(3):1120-8
AD - Department of Endocrinology, Medical Research Center, Polish Academy of
Sciences, 02-097 Warsaw, Poland. monika@amwaw.edu.pl
TRs are transcription factors that regulate cell proliferation,
differentiation, and apoptosis. They are cellular homologs of the
transcriptionally inactive viral oncogene v-erbA. We tested the
hypothesis that the functions of TRs could be impaired in cancer tissues
as a result of aberrant expression and/or somatic mutations. As a model
system, we selected human thyroid papillary cancer, in which the most
common abnormalities, RET/papillary thyroid cancer rearrangements
(fusion of RET kinase domain to the activating domains of other genes),
were found in 40--45% of cases. We found that the mean expression levels
of TR beta mRNA and TR alpha mRNA were significantly lower, whereas the
protein levels of TR beta 1 and TR alpha 1 were higher in cancer tissues
than in healthy thyroid. Sequencing of TR beta 1 and TR alpha 1 cDNAs,
cloned from 16 papillary cancers, revealed that mutations affected
receptor amino acid sequences in 93.75% and 62.5% of cases,
respectively. In contrast, no mutations were found in healthy thyroid
controls, and only 11.11% and 22.22% of thyroid adenomas had such TR
beta 1 or TR alpha 1 mutations, respectively. The majority of the
mutated TRs lost their trans-activation function and exhibited dominant
negative activity. These findings suggest a possible role for mutated
thyroid hormone receptors in the tumorigenesis of human papillary
thyroid carcinoma.
14
UI - 11889192
AU - Shih A; Davis FB; Lin HY; Davis PJ
TI -
Resveratrol induces apoptosis in thyroid cancer cell lines via a MAPK-
and p53-dependent mechanism.
SO - J Clin Endocrinol Metab 2002 Mar;87(3):1223-32
AD - Medical Research Service, Stratton Veterans Affairs Medical Center,
Albany, New York 12208, USA.
Two papillary thyroid carcinoma (PTC) and two follicular thyroid
carcinoma (FTC) cell lines treated with resveratrol (RV), 1-10 microM,
showed activation and nuclear translocation of MAPK (extracellular
signal-regulated kinase 1/2). Cellular abundance of the oncogene
suppressor protein p53, serine phosphorylation of p53, and abundance of
c-fos, c-jun, and p21 mRNAs were also increased by RV. Inhibition of the
MAPK pathway by either H-ras antisense transfection or PD 98059, an MAPK
kinase inhibitor, blocked these RV-induced effects. Addition of
pifithrin-alpha, a specific inhibitor of p53, or transfection of p53
antisense oligonucleotides caused decreased RV-induced p53 and p21
expression in PTC and FTC cells. Studies of nucleosome levels estimated
by ELISA and of DNA fragmentation showed that RV induced apoptosis in
both papillary and follicular thyroid cancer cell lines; these effects
were inhibited by pifithrin-alpha and by p53 antisense oligonucleotide
transfection. PD 98059 and H-ras antisense transfection also blocked
induction of apoptosis by RV. Thus, RV acts via a Ras-MAPK kinase-MAPK
signal transduction pathway to increase p53 expression, serine
phosphorylation of p53, and p53-dependent apoptosis in PTC and FTC cell
lines.
15
UI - 11889211
AU - D'Elia AV; Tell G; Russo D; Arturi F; Puglisi F; Manfioletti G; Gattei
TI -
V; Mack DL; Cataldi P; Filetti S; Di Loreto C; Damante G
Expression and localization of the homeodomain-containing protein HEX in
human thyroid tumors.
SO - J Clin Endocrinol Metab 2002 Mar;87(3):1376-83
AD - Dipartimento di Scienze e Tecnologie Biomediche, Universita di Udine,
33100 Udine, Italy.
Homeobox genes are involved in neoplastic transformation of both
epithelial and hemopoietic tissues. The divergent homeobox gene HEX is
expressed in the anterior visceral endoderm during early mouse
development and in some adult tissues of endodermal origin, including
liver and thyroid. Whereas a role in leukemyogenesis has been proposed
already, few data are available on the involvement of HEX in human
epithelial tumors. Herein, we analyzed HEX expression and subcellular
localization in a series of 55 human thyroid tumors and in several
tumoral cell lines. HEX mRNA was detected by RT-PCR either in normal
tissues or in thyroid adenomas and differentiated (papillary and
follicular) carcinomas. HEX mRNA was also expressed in most
undifferentiated carcinomas. Subcellular localization of HEX protein was
investigated by immunohistochemistry. In normal tissues and adenomas,
HEX protein was present both in nucleus and cytoplasm. In contrast, both
differentiated and undifferentiated carcinomas, as well as the tumoral
cell lines investigated, showed HEX protein only in the cytoplasm. These
findings suggest that regulation of HEX entry in the nucleus of
thyrocytes may represent a critical step during human thyroid
tumorigenesis.
16
UI - 11762820
AU - Freyer G; Ligneau B; Schlumberger M; Blandy C; Contedevolx B;
TI -
Trillet-Lenoir V; Lenoir GM; Chau N; Dazord A
Quality of life in patients at risk of medullary thyroid carcinoma and
followed by a comprehensive medical network: trends for future
evaluations.
SO - Ann Oncol 2001 Oct;12(10):1461-5
AD - Medical Oncology Unit, Centre Hospitalier Lyon-Sud, and EA 643,
Universite Lyon I, France. Gilles.Freyer@chu-lyon.fr
BACKGROUND: As shown in a previous study, the knowledge of the genetic
risk in individuals belonging to families at risk of medullary-thyroid
carcinoma (MTC) could be associated with impaired quality of life (QoL).
PATIENTS AND METHODS: In the present study, we compared the QoL scores
obtained in the same period with the subjective quality of life profile
(SQLP): in 82 individuals at risk of MTC who had been tested for
Ret-mutations; in 200 women at risk of familial breast/ovarian cancer
syndrome (BOC); and in a control population of 3,501 healthy volunteers.
RESULTS: Significant differences were observed in favour of healthy
volunteers as well as individuals at risk of MTC, over women at risk of
BOC (mean scores: 0.89, 0.85, and 0.64, respectively, P < or = 0.001),
but QoL scores were not statistically different between individuals at
risk of MTC and the control population (P = 0.2). However, they were
significantly inferior in the subgroup of germline Ret-mutation
carriers, as compared to the control population (mean scores: 0.73 and
0.89, P = 0.04). In the latter, the relationships with the children and
the family were the most important facets of their QoL. CONCLUSION: Our
results confirm the potentially negative impact of the knowledge of the
genetic risk of cancer and its consequences in terms of morbidity and
follow-up, on the QoL in people followed at oncogenetic visits.
17
UI - 11881248
AU - Sokolowski E
TI -
[Consequences of the Chernobyl accident are difficult to prove. Thyroid
gland cancer among those who were exposed to radiation during childhood
is the only disease evidently connected to the radiation so far]
SO - Lakartidningen 2002 Jan 31;99(5):418-20
18
UI - 11888879
AU - Stojadinovic A; Hoos A; Ghossein RA; Urist MJ; Leung DH; Spiro RH; Shah
TI -
JP; Brennan MF; Singh B; Shaha AR
Hurthle cell carcinoma: a 60-year experience.
SO - Ann Surg Oncol 2002 Mar;9(2):197-203
AD - Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York,
New York, USA.
BACKGROUND: The aim of this study was to define the clinical behavior
and prognostic indicators of outcome in Hurthle cell cancer (HCC).
METHODS: Diagnosis was confirmed for 56 patients with HCC treated
between 1940 and 2000, who form the basis of this study. Primary end
points were relapse-free survival (RFS) and disease-specific survival
(DSS). Data were analyzed with the Kaplan-Meier method and by log-rank
test. RESULTS: The extent of thyroid resection did not predict outcome.
Recurrence was a significant predictor of tumor-related mortality.
Significant adverse predictors of RFS and DSS were degree of invasion,
size >4 cm, extrathyroidal extension, and initial nodal or distant
metastases. The most significant predictor of outcome was extent of
invasion. Eight-year RFS values for low- and high-risk groups were 100%
and 24%. Corresponding rates of 8-year DSS were 100% and 58%.
CONCLUSIONS: Widely invasive HCC is an aggressive malignancy that
identifies patients who are at high risk for recurrence and
tumor-related death. Patients with HCC have a prognosis that is reliably
predicted by degree of invasion, tumor size, extrathyroidal disease
extension, and initial nodal or distant metastasis. Recurrence portends
a poor outcome. High-risk patients and those with recurrence should be
considered for adjuvant therapy.
19
UI - 11832639
AU - Mishra A; Mishra SK
TI -
Thyroid nodules in Graves' disease: implications in an endemically
iodine deficient area.
SO - J Postgrad Med 2001 Oct-Dec;47(4):244-7
AD - Department of Endocrine Surgery, Sanjay Gandhi Post-Graduate Institute
of Medical Sciences, Lucknow - 226 014, India.
BACKGROUND AND AIM: The presence of thyroid nodules with Graves' disease
raises concern about co-existent thyroid malignancy. The objective of
this study is to evaluate the risk of thyroid carcinoma and the need for
surgical intervention in, patients with Graves' disease with co-existent
nodules in an endemically iodine deficient area (IDA). SUBJECTS AND
METHODS: Retrospective study of 130 surgically managed patients of
Graves' disease (1990-1999). Out of these 35 (26.9%) cases had palpable
nodules. No patient had history of previous head and neck irradiation or
radioiodine therapy. The clinico-pathological findings and follow-up of
these cases were noted. RESULTS: Mean age of patients with nodules was
40.2 +/- 9.5 years and male to female ratio was 1:2.2. The overall
incidence of thyroid carcinoma in Graves' disease was 6.2% (8/130
cases), while the incidence, in cases having nodule with Graves' disease
was 17.1% (6/35 cases). The median age of patients with carcinoma was 45
years (5 women and 1 man). Besides laboratory investigations for
hyperthyroidism, preoperative investigations included fine needle
aspiration cytology (FNAC) and thyroid scintigraphy in 29 and 25 cases
respectively. Incidence of malignancy in palpable cold nodules was 20%.
FNAC could not predict malignancy with certainty in any of these cases.
Five patients had papillary thyroid carcinoma while one had follicular
carcinoma. Median tumour diameter was 10 mm. Tumour was multi-centric in
two cases while one case had metastases to cervical lymph node. In
follow-up (median =5.5 years) one patient died of unrelated cause, while
rest are alive with no evidence of disease. CONCLUSIONS: Nodules are
frequently associated with Graves' disease in IDA. Incidence of
carcinoma is high in palpable cold nodule. We recommend early
thyroidectomy in these cases.
20
UI - 11842375
AU - Harach HR; Sanchez SS; Williams ED
TI -
Pathology of the autonomously functioning (hot) thyroid nodule.
SO - Ann Diagn Pathol 2002 Feb;6(1):10-9
AD - Services of Pathology and Surgery, "Dr A. Onativia" Endocrinology and
Metabolism Hospital, Salta, Argentina.
We describe the pathologic findings of 73 clinically and
scintigraphically confirmed hot nodules. In general, hot nodules from an
unselected group primarily treated by surgery were smaller and the sex
ratio was closer to equality compared with the ample female predominance
in the referral, pre-, and post-prophylaxis groups. Malignancy was
observed in six cases (8.2%) (5 follicular, 1 papillary). Of the 67
benign tumors, 48 (71.6%) were adenomas which showed the
cytoarchitectural features of hot nodules described previously, and 19
(28.3%) were less well-differentiated adenomas that included a few
oxyphil tumors. Intracolloid oxalate crystals from background thyroid
tissue were present in 59 assessable cases (83%) overall, the majority
showed more than occasional crystals that had a tendency to increase in
number with decreasing morphologic activity of the thyroid epithelium.
Thyroglobulin protein and mRNA stainings tended to be more pronounced in
cell cytoplasm of the tumors than in background thyroid. This study
shows that hot nodules may show a wide morphologic spectrum of
follicular neoplasms and can be occasionally malignant. It is inferred
from the morphologic and other findings that it is likely that some, if
not all, of the primary follicular cancers associated with hyperfunction
arise by clonal progression from benign hot nodules. This progression is
rare, probably because most hot nodules present with the symptoms of
hyperfunction and receive early treatment. Copyright 2002 by W.B.
Saunders Company
21
UI - 11891946
AU - Absher KJ; Truong LD; Khurana KK; Ramzy I
TI -
Parathyroid cytology: avoiding diagnostic pitfalls.
SO - Head Neck 2002 Feb;24(2):157-64
AD - Department of Pathology, Baylor College of Medicine, One Baylor Plaza,
Houston, TX 77030, USA. iramzy@bcm.tmc.edu
BACKGROUND: Interpretation of parathyroid fine-needle aspirates (FNA)
remains problematic not only because this type of specimen is rare but
also because the pertinent literature is very limited. We systematically
reviewed parathyroid FNAs in our files and sought to delineate
additional diagnostic criteria. DESIGN: Review of all thyroid and
parathyroid lesions. The final diagnoses included four parathyroid
adenomas, one intrathyroidal hyperplastic parathyroid, one
intrathyroidal parathyroid adenoma, one atypical parathyroid adenoma
(all confirmed by histologic screening or immunocytochemistry), and five
parathyroid cysts (all confirmed by immunoassay). Papanicolaou and Diff
Quik-stained smears of the parathyroid FNAs were reviewed. The cytologic
features were compared and contrasted with those of thyroid FNAs to
establish criteria for differential diagnoses. RESULTS: The FNAs of the
five parathyroid cysts yielded virtually acellular fluid with a
characteristic water-clear appearance and markedly elevated levels of
parathyroid hormone. The remaining seven aspirates consisted of
moderately cellular smears that showed an admixture of architectural
features. Common patterns included cohesive three-dimensional groups,
disorganized sheets, papillary fragments, microfollicles, and a single
case showing lymphoidlike smears. Although the cells were generally
small and round to oval, all cases demonstrated mild to moderate
anisokaryosis. The nuclei were hyperchromatic E with coarsely granular
chromatin reminiscent of that of small lymphocytes. Occasional nucleoli
were noted. Although the cytoplasm was usually pale blue and finely
granular with ill-defined borders, two cases showed well-delineated
cytoplasmic membranes. Less common findings included cytoplasmic
granulation, vacuolization, and rare oxyphilic cells. Naked nuclei were
noted in the background of all of the aspirates to varying degrees.
Other background findings included the presence of colloidlike material,
macrophages, and lymphocytes. One interesting finding that to date has
not been reported is the presence of nuclear overlapping (100%) and
nuclear molding (71%), which is an uncommon finding in thyroid
aspirates. CONCLUSIONS: FNAs of the parathyroid can be easily confused
with that of the thyroid, not only because of the clinical similarity
between these two types of lesions but also because of the overlap in
cytomorphologic features of the aspirated cells. Although no one single
cytomorphologic feature is diagnostic, a combination of cytologic
parameters noted earlier should raise the possibility of a parathyroid
lesion. Aspirates of parathyroid cysts show acellular water-clear fluid
with elevated parathyroid hormone measurements. Copyright 2002 John
Wiley & Sons, Inc.
22
UI - 11870476
AU - Berczi C; Mezosi E; Galuska L; Varga J; Bajnok L; Lukacs G; Balazs G
TI -
Technetium-99m-sestamibi/pertechnetate subtraction scintigraphy vs
ultrasonography for preoperative localization in primary
hyperparathyroidism.
SO - Eur Radiol 2002 Mar;12(3):605-9
AD - First Department of Surgery, P.O. Box 27, University of Debrecen,
Hungary 1, Nagyerdei str. 98, 4012 Debrecen, Hungary.
berczi@jaguar.dote.hu
A prospective study was performed to evaluate the efficacy of
technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction
scanning and US for imaging parathyroid glands in primary
hyperparathyroidism. Sixty-three patients were surgically treated for
primary hyperparathyroidism (HPT). Preoperative scintigraphy and US were
performed in all cases. Bilateral neck exploration was carried out on
each patient. Results of radionuclide studies and US were compared with
surgical and histological findings. In 57 patients with primary HPT the
radionuclide scanning gave true-positive results. Four false-negative
and two false-positive scintigrams were obtained. The sensitivity and
the positive predictive value (PPV) of scintigraphy were 93 and 97%,
respectively. Forty-one cases were correctly localized by the US.
Seventeen US results were false negative and five were false positive.
The sensitivity and the PPV for US were 71 and 89%, respectively. There
was a statistically significant difference between the sensitivity of
the scintigraphy compared with the US ( p=0.001). Sensitivities of
radionuclide scans and US were higher for adenomas (100 and 83%) than
for hyperplastic glands (75 and 40%). The sensitivity of
technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction
scintigraphy was significantly higher compared with US. This sensitive
method could help surgeons in performing a rapid and directed
parathyroidectomy.
23
UI - 11891962
AU - Stoler DL; Datta RV; Charles MA; Block AW; Brenner BM; Sieczka EM; Hicks
TI -
WL Jr; Loree TR; Anderson GR
Genomic instability measurement in the diagnosis of thyroid neoplasms.
SO - Head Neck 2002 Mar;24(3):290-5
AD - Department of Experimental Pathology, Roswell Park Cancer Institute,
Buffalo, New York, USA.
BACKGROUND: Clinically palpable thyroid nodules are present in
approximately 10% of the population, although only 5% to 7% of these
nodules harbor malignancy. Fine-needle aspiration has become one of the
central tools in the diagnostic armamentarium of the
surgeon/endocrinologist. There is, however, up to a 30% indeterminate
diagnostic rate associated with this technique, resulting in unnecessary
surgical interventions for patients harboring benign disease. A second
issue of clinical importance is the unreliability of predicting outcomes
based either on histologic findings alone or in combination with
clinical staging. To address these diagnostic and clinical shortcomings,
we have used measurement of genomic instability as a diagnostic and
prognostic indicator for thyroid neoplasms. METHODS: Genomic instability
of thyroid tissue samples was determined by inter-(simple sequence
repeat) PCR, microsatellite instability analysis, and fluorescence in
situ hybridization (FISH) on thyroid neoplasms from 22 patients.
RESULTS: Inter-(simple sequence repeat) PCR detected genomic instability
with an index range 0% to 1.9% (mean, 0.56%) in patients with benign
disease, whereas in patients with malignant histologic findings the
values ranged from 0% to 6.6% (mean, 2.9%). This difference between
benign and malignant values was statistically significant (p =.004).
There was no demonstrable microsatellite instability or loss of
heterozygosity for six markers examined in this group. Losses of
chromosomes 17 and X in benign disease and gains of chromosomes 7, 12,
17, and X in Hurthle cell carcinoma were observed, although not at a
significant rate. CONCLUSIONS: Genomic instability as measured by
inter-(simple sequence repeat) PCR was significantly higher for
malignant diseases compared with benign thyroid tissues, but no such
association was seen with aneuploidy or microsatellite instability.
Copyright 2002 Wiley Periodicals, Inc.
24
UI - 11919168
AU - Grimm D; Bauer J; Kossmehl P; Shakibaei M; Schoberger J; Pickenhahn H;
TI -
Schulze-Tanzil G; Vetter R; Eilles C; Paul M; Cogoli A
Simulated microgravity alters differentiation and increases apoptosis in
human follicular thyroid carcinoma cells.
SO - FASEB J 2002 Apr;16(6):604-6
AD - Institute of Clinical Pharmacology and Toxicology, Benjamin Franklin
Medical Center, Freie Universitat Berlin, Germany.
dgrimm@zedat.fu-berlin.de
This study focuses on the effects of simulated microgravity (0g) on the
human follicular thyroid carcinoma cell line ML-1. Cultured on a
three-dimensional clinostat, ML-1 cells formed three-dimensional MCTSs
(MCTS diameter: 0.3 +/- 0.01 mm). After 24 and 48 h of clinorotation,
the cells significantly decreased fT3 and fT4 secretion but up-regulated
the thyroid-stimulating hormone-receptor expression as well as the
production of vimentin, vinculin, and extracellular matrix proteins
(collagen I and III, laminin, fibronectin, chondroitin sulfate) compared
with controls. Furthermore, ML-1 cells grown on the clinostat showed
elevated amounts of the apoptosis-associated Fas protein, of p53, and of
bax but showed reduced quantities of bcl-2. In addition, signs of
apoptosis became detectable, as assessed by terminal deoxynucleotidyl
transferase-mediated dUTP digoxigenin nick end labeling, 4',
6-diamidino-2-phenylindole staining, DNA laddering, and 85-kDa
apoptosis-related cleavage fragments. These fragments resulted from
enhanced 116-kDa poly(ADP-ribose)polymerase (PARP) activity and
apoptosis. These observations suggest that clinorotation elevates
intermediate filaments, cell adhesion molecules, and extracellular
matrix proteins and simultaneously induces apoptosis in follicular
thyroid cancer cells. In conclusion, our experiments could provide a
regulatory basis for the finding that astronauts show low thyroid
hormone levels after space flight, which may be explained by the
increase of apoptosis in thyrocytes as a result of simulated 0g.
25
UI - 11799311
AU - Hadjieva T
TI -
Scoring patients' risk in differentiated thyroid cancer.
SO - Onkologie 2001 Dec;24(6):561-8
AD - Radiotherapy Department, University Hospital Queen Giovanna, Faculty of
Medicine, Sofia, Bulgaria. rad@cserv.mgu.bg
BACKGROUND: Despite of excellent long-term results, there is a need for
the selection of patients with differentiated thyroid cancer who
experience an unfavorable outcome. PATIENTS AND METHODS: Between 1980
and 1997, 406 patient
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