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Abramson Cancer CenterNCI CANCERLIT® Search: Endometrial Cancer - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
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.
2
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. pierre-yves.marcy@cal.nice.fnclcc.fr
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.
3
UI - 11781515
AU - Zaino RJ
TI -
The fruits of our labors: distinguishing endometrial from endocervical
adenocarcinoma.
SO - Int J Gynecol Pathol 2002 Jan;21(1):1-3
4
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.
5
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.
6
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.
7
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.
8
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.
9
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. laurie.elit@hrcc.on.ca
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.
10
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.
wnaumann@mindspring.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.
11
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.
12
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.
onkologia@gin.cm-uj.krakow.pl
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.
13
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.
14
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. cnakagawa@ob-gy.med.tohoku.ac.jp
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.
15
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.
16
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.
17
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.
18
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.
19
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.
20
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.
21
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.
22
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. hadaczek@poczta.onet.pl
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.
23
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.
24
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.
steiner@mail.uni-mainz.de
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.
25
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
26
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
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