abstract: Hormone Therapy and Different Ovarian Cancers: A National Cohort Study (postmenopausal women/does not include reference to clear cell ovarian)

 Blogger's Note: the abstract makes no reference to clear cell ovarian, given the number of women followed this omission (in the abstract) is curious


Hormone Therapy and Different Ovarian Cancers: A National Cohort Study

Abstract

Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. 

Using Danish national registers, the authors identified 909,946 women who were followed from 1995–2005. The women were 50–79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. 

Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers, including information about tumor histology......... In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. 

Compared with never users, women taking unopposed oral estrogen therapy had increased risks of both serous tumors and endometrioid tumors but decreased risk of mucinous tumors. Similar increased risks of serous and endometrioid tumors were found with estrogen/progestin therapy, whereas no association was found with mucinous tumors. 

Consistent with results from recent cohort studies, the authors found that ovarian cancer risk varied according to tumor histology. The types of ovarian tumors should be given attention in future studies.

abstract: Endometriosis does not confer improved prognosis in ovarian carcinoma of uniform cell type.

Endometriosis does not confer improved prognosis in ovarian carcinoma of uniform cell type [Am J Surg Pathol. 2012]

Abstract

The role of endometriosis in ovarian cancer, disease progression, and survival is a subject of active investigation. A series of 144 ovarian cancers with clear cell or endometrioid histology or associated endometriosis, all classified on the basis of strict histologic criteria, was evaluated to further explore the relationship between endometriosis-associated ovarian cancer and age at presentation, FIGO stage, histology, presence of synchronous primary disease elsewhere in the mullerian tract, and survival.

Patients with endometrioid carcinomas were significantly younger (mean, 52 y) in comparison with patients with either clear cell carcinoma (mean, 55 y) or mixed tumors (mean, 59 y; P=0.002).

Clear cell carcinoma presented as low-stage disease (FIGO I) in 33% of cases compared with endometrioid carcinomas in 97% of cases and mixed carcinomas in 27% of cases. Endometriosis was associated with 53% of clear cell carcinomas, 33% of endometrioid carcinomas, and 45% of mixed tumors (P<0.001). Synchronous primary tumors, observed in 31% of endometrioid tumors, 5% of mixed tumors, and in 2% of clear cell tumors (P<0.001), were unlikely to be associated with endometriosis (P=0.04). Univariate analysis of the aggregate cohort demonstrated that the single best overall predictor of disease-free survival was FIGO stage at presentation (P<0.001), followed by histologic subtype (P=0.003).

Endometriosis did not have a significant relationship with disease-free survival (P=0.7). We conclude that the link between endometriosis and ovarian cancer is much stronger for clear cell carcinoma than for other histologic subtypes (P<0.001). Furthermore, when uniform histologic criteria are applied, true mixed endometrioid and clear cell carcinomas are uncommon; most endometriosis-associated mixed tumors are heterogenous mixtures of endometrioid, mucinous, and serous histology with areas of clear cell cytoplasm. Endometriosis per se does not appear to predict prognosis in clear cell and endometrioid tumors, with the possible exception of tumors with mixed histology. Until more data are collected, pathologists should classify ovarian tumors with mixed histology as a separate and potentially unique biological and prognostic group.

(Apr 2012) Commentary: Link between endometriosis and ovarian-cancer subtypes : The Lancet Oncology

Link between endometriosis and ovarian-cancer subtypes : The Lancet Oncology

"Previous large epidemiological studies have attempted to identify benign gynaecological disorders that predispose to the development of epithelial ovarian cancer. The only disorder that has been repeatedly1—4 (although not universally5) associated with this cancer is endometriosis. Results of some of these studies have suggested a specific link with endometrioid and clear-cell ovarian cancers, but until now none had the power to allow definitive subgroup analysis based on a contemporary definition of histological subtype.

 

In a study reported in the Lancet Oncology, Celeste Leigh Pearce and colleagues6 assessed self-reported endometriosis data from 13 pooled case—control studies in the Ovarian Cancer Association Consortium (OCAC). They confirm that a history of endometriosis is significantly associated with an increased risk of clear-cell (odds ratio 3·05, 95% CI 2·43—3·84) and endometrioid (2·04, CI 1·67—2·48) ovarian cancers, and for the first time show an association with low-grade serous ovarian cancer (2·11, 1·39—3·20). No association was noted between endometriosis and high-grade serous, mucinous, serous borderline, or mucinous borderline ovarian cancers.

 

With more than 23 000 participants (7911 with a diagnosis of ovarian cancer), the main strengths of this study are its statistical power and its robust methods. Incidences of reported endometriosis differ substantially between the pooled studies. Although clinicopathological and genetic differences between the populations could reasonably be expected, importantly there was no significant heterogeneity of the association with histological subtype in the different studies.

The main truly novel finding is an association between a history of endometriosis and low-grade serous ovarian cancer. Perhaps surprisingly, serous borderline tumours (from which invasive low-grade serous ovarian cancers are believed to arise7) are not also associated with a history of endometriosis.

abstract: Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies : The Lancet Oncology

Background

Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer.

 Interpretation

Clinicians should be aware of the increased risk of specific subtypes of ovarian cancer (clear cell, endometrioid) in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer.

abstract: A rare case of the coexistence of ovarian clear cell carcinoma, mucinous cystadenoma, and endometriosis in the same ovary (Taiwan)

Abstract

Clear cell carcinomas and endometrioid carcinomas are associated with endometriosis. The association of clear cell carcinomas with mucinous lesions has only been reported infrequently, and with mucinous cystadenoma has been rarely reported.

This is the second reported case of the coexistence of ovarian clear cell carcinoma, mucinous cystadenoma, and endometriosis in the same ovary.

A 57-year-old woman presented with lower abdominal pain for three weeks. Ultrasonography revealed a 16 x 14 x 10 cm mass in the left ovary with solid and cystic components. Hysterectomy and bilateral salpingo-oophorectomy were performed. Histopathological examination of the left ovary revealed the presence of clear cell carcinoma, mucinous cystadenoma, and endometriosis. Continuity between the areas of mucinous epithelium and clear cell carcinoma were noted; this may suggest that clear cell carcinoma may arise from endometriosis or mucinous cystic tumors.

Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features.

Abstract

Malignant epithelial tumors (carcinomas) are the most common ovarian cancers and also the most lethal gynecological malignancies.
Based on histopathology and molecular genetic alterations, ovarian carcinomas are divided into five main types (high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3%), and low-grade serous carcinomas (5%)) that account for over 95% of cases.

These types are essentially distinct diseases, as indicated by differences in epidemiological and genetic risk factors, precursor lesions, patterns of spread, and molecular events during oncogenesis, response to chemotherapy, and prognosis. For a successful specific treatment, reproducible histopathological diagnosis of the tumor cell type is critical.

The five tumor types are morphologically diverse and resemble carcinomas of the uterus. Actually, recent investigations have demonstrated that a significant number of cancers, traditionally thought to be primary ovarian tumors (particularly serous, endometrioid, and clear cell carcinomas), originate in the fallopian tube and the endometrium and involve the ovary secondarily. This review summarizes recent advances in the molecular pathology which have greatly improved our understanding of the biology of ovarian carcinoma and are also relevant to patient management.

abstract: KRAS mutations in ovarian low-grade endometrioid adenocarcinoma: association with concurrent endometriosis (study of KRAS/BRAF mutations)

Summary

The association between ovarian endometrioid adenocarcinoma and endometriosis is well established. However, not all endometrioid adenocarcinomas are directly related to endometriosis, and it has been suggested that there may be clinicopathologic differences between endometriosis-positive and endometriosis-negative tumors. Molecular alterations in endometrioid adenocarcinoma include KRAS and BRAF mutations, but the incidence of these abnormalities in previous reports has been highly variable (0%-36% and 0%-24%, respectively).....

Keywords

• Ovary;
• Endometrioid;
• Adenocarcinoma;
• Endometriosis;
• Molecular

Correspondence: Authors' response: 'Focusing on HER2 as a potential therapeutic target in primary ovarian mucinous carcinomas' (includes stats on serous/endometrioid/clear cell/mucinous)

Blogger's Note: without a subscription ($$$), the following is available for viewing:

Authors' response: 'Focusing on HER2 as a potential therapeutic target in primary ovarian mucinous carcinomas':
In a study involving a large series of epithelial ovarian carcinomas (EOCs), McCaughan et al1 reported human epidermal growth factor receptor 2 (HER2) protein overexpression and amplification in all major histological subtypes, an observation consistent with the literature.2 3 Specifically, they document HER2 gene amplification in 3.0% (7/259) of serous papillary carcinomas, 2.1% (2/92) of endometrioid carcinomas, 25.0% (3/12) of mucinous carcinomas, 4.0% (1/25) of clear cell carcinomas and 11.9% (7/60) of mixed type carcinomas. Although their number of mucinous carcinomas was low (n=12), the higher prevalence of HER2 gene amplification relative to the other histological subtypes is also consistent with the literature.4 5
We had previously reported similar findings of primary ovarian mucinous carcinomas having the highest prevalence of HER2 genomic amplification and protein overexpression among the various EOC histological subtypes and had proposed that ovarian mucinous carcinomas represent a...

Ovarian Endometrioid Adenocarcinoma: Incidence and Clinical Significance of the Morphologic and Immunohistochemical Markers of Mismatch Repair Protein Defects and Tumor Microsatellite Instability

"Ovarian cancer, particularly endometrioid (cell type)adenocarcinoma, is also associated with Lynch syndrome.....Overall, 10% of tumors had abnormal MMR protein status, defined as complete immunohistochemical loss of expression of MLH1, MSH2, MSH6, and/or PMS2.....Concurrent uterine tumor was present in 5/7 patients whose ovarian tumor had abnormal MMR/MSI.......Although abnormal MMR/MSI did not carry prognostic value in this study, it did predict the involvement of the uterus by the tumor. Thus, in patients with ovarian endometrioid adenocarcinoma who undergo uterus-sparing surgery, abnormal MMR/MSI should prompt further diagnostic evaluation of the endometrium for tumor."

 

Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

Background: Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization. 

Methods: We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers. 

There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67%; mucinous: 1%; endometrioid: 12%; clear-cell: 2%). 

Loss of ARID1A-Associated Protein Expression is a Frequent Event in Clear Cell and Endometrioid Ovarian Cancers

Abstract

Background: Inactivating somatic mutations in the ARID1A gene are described in a significant fraction of clear cell and endometrioid ovarian cancers leading to loss of the corresponding protein (BAF250a).

Conclusions:

These data confirm that loss of the ARID1A-encoded protein BAF250a is a frequent event in the genesis of clear cell and endometrioid ovarian cancers. Loss of BAF250a was not associated with clinical or epidemiologic characteristics. One explanation for these findings is that inactivation of the chromatin remodeling pathway may be a requisite event in the development of these cancers.

abstract: The association between endometriosis and gynecological cancers and breast cancer: A review of epidemiological data

CONCLUSIONS:

Endometriosis seems to be a precursor of epithelial ovarian cancer, especially clear cell and endometrioid adenocarcinomas. However, current evidence is insufficient to draw any definitive conclusions whether this association represents causality or the sharing of similar risk factors and/or antecedent mechanisms

repost (abstract) - Gynecologic Oncology : Ovarian cancer linked to lynch syndrome typically presents as early-onset, non-serous epithelial tumors

Research highlights

► Lynch syndrome-associated ovarian cancer develops at early age (mean 48 years) with half of the tumors diagnosed at early stage and an overrepresentation of endometrioid (35%) and clear cell (17%) histologies.
► MMR gene mutations affect MSH2 in 49%, MSH6 in 33% and MLH1 in 17% with immunohistochemical loss of MMR protein staining in 92%

Search Results: 'endometrioid' 'ovarian' 2011 ASCO Abstracts

Find ALL words: endometrioid ovarian

Found 11 documents

abstract: Calculator for ovarian carcinoma subtype prediction : Modern Pathology

Abstract:

With the emerging evidence that the five major ovarian carcinoma subtypes (high-grade serous, clear cell, endometrioid, mucinous, and low-grade serous) are distinct disease entities, management of ovarian carcinoma will become subtype specific in the future.

In an effort to improve diagnostic accuracy, we set out to determine if an immunohistochemical panel of molecular markers could reproduce consensus subtype assignment.

Immunohistochemical expression of 22 biomarkers were examined on tissue microarrays constructed from 322 archival ovarian carcinoma samples from the British Columbia Cancer Agency archives, for the period between 1984 and 2000, and an independent set of 242 cases of ovarian carcinoma from the Gynaecologic Tissue Bank at Vancouver General Hospital from 2001 to 2008. Nominal logistic regression was used to produce a subtype prediction model for each of these sets of cases. These models were then cross-validated against the other cohort, and then both models were further validated in an independent cohort of 81 ovarian carcinoma samples from five different centers.

Starting with data for 22 markers, full model fit, backwards, nominal logistic regression identified the same nine markers (CDKN2A, DKK1, HNF1B, MDM2, PGR, TFF3, TP53, VIM, WT1) as being most predictive of ovarian carcinoma subtype in both the archival and tumor bank cohorts. These models were able to predict subtype in the respective cohort in which they were developed with a high degree of sensitivity and specificity (κ statistics of 0.88±0.02 and 0.86±0.04, respectively).

When the models were cross-validated (ie using the model developed in one case series to predict subtype in the other series), the prediction equation's performances were reduced (κ statistics of 0.70±0.04 and 0.61±0.04, respectively) due to differences in frequency of expression of some biomarkers in the two case series. Both models were then validated on the independent series of 81 cases, with very good to excellent ability to predict subtype (κ=0.85±0.06 and 0.78±0.07, respectively).

A nine-marker immunohistochemical maker panel can be used to objectively support classification into one of the five major subtypes of ovarian carcinoma.

open access journal: Journal of Ovarian Research Differential hRad17 expression by histologic subtype of ovarian cancer

Background
In the search for unique ovarian cancer biomarkers, ovarian specific cDNA microarray analysis identified hRad17, a cell cycle checkpoint protein, as over-expressed in ovarian cancer. The aim of this study was to validate this expression.

Methods
Immunohistochemistry was performed on 72 serous, 19 endometrioid, 10 clear cell, and 6 mucinous ovarian cancers, 9 benign ovarian tumors, and 6 normal ovarian tissue sections using an anti-hRad17 antibody. Western blot analysis and quantitative PCR were performed using cell lysates and total RNA prepared from 17 ovarian cancer cell lines and 6 normal ovarian epithelial cell cultures (HOSE).


Results
Antibody staining confirmed upregulation of hRad17 in 49.5% of ovarian cancer cases. Immunohistochemistry demonstrated that only 42% of serous and 47% of endometrioid subtypes showed overexpression compared to 80% of clear cell and 100% of mucinous cancers.

Conclusions
hRad17 is over-expressed in ovarian cancer. This over-expression varies by subtype suggesting a role in the pathogenesis of these types. Functional studies are needed to determine the potential role of this protein in ovarian cancer.

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abstract: Mutation and Loss of Expression of ARID1A in Uterine Low-grade Endometrioid Carcinoma

Abstract:

ARID1A is a recently identified tumor suppressor gene that is mutated in approximately 50% of ovarian clear cell and 30% of ovarian endometrioid carcinomas. The mutation is associated with loss of protein expression as assessed by immunohistochemistry.

In this study, we evaluated ARID1A immunoreactivity in a wide variety of carcinomas to determine the prevalence of ARID1A inactivation in carcinomas. Mutational analysis of ARID1A was carried out in selected cases. Immunoreactivity was not detected (corresponding to inactivation or mutation of ARID1A) in 36 (3.6%) of 995 tumors.

Uterine low-grade endometrioid carcinomas showed a relatively high-frequency loss of ARID1A expression, as 15 (26%) of 58 cases were negative. The other tumor that had a relatively high-frequency loss of ARID1A expression was gastric carcinoma (11%). Mutational analysis showed 10 (40%) of 25 uterine endometrioid carcinomas; none of 12 uterine serous carcinomas and none of 56 ovarian serous and mucinous carcinomas harbored somatic ARID1A mutations. All mutations in endometrioid carcinomas were nonsense or insertion/deletion mutations, and tumors with ARID1A mutations showed complete loss or clonal loss of ARID1A expression.

In conclusion, this study is the first large-scale analysis of a wide variety of carcinomas showing that uterine low-grade endometrioid carcinoma is the predominant tumor type harboring ARID1A mutations and frequent loss of ARID1A expression. These findings suggest that the molecular pathogenesis of low-grade uterine endometrioid carcinoma is similar to that of ovarian low-grade endometrioid and clear cell carcinoma, tumors that have previously been shown to have a high-frequency loss of expression and mutation of ARID1A.

abstract: Ovarian cancer linked to lynch syndrome typically presents as early-onset, non-serous epithelial tumors (endometrioid/clear cell cell types) MSH2 MSH6 MLH1

Ovarian cancer linked to lynch syndrome typically presents as early-onset, non-serous epithelial tumors.

Abstract

OBJECTIVE: Heredity is a major cause of ovarian cancer and during recent years the contribution from germline mismatch repair (MMR) gene mutations linked to Lynch syndrome has gradually been recognized.

METHODS: We characterized clinical features, tumor morphology and mismatch repair defects in all ovarian cancers identified in Swedish and Danish Lynch syndrome families.

RESULTS: In total, 63 epithelial ovarian cancers developed at mean 48 (range 30-79) years of age with 47% being early stage (FIGO stage I). Histologically, endometrioid (35%) and clear cell (17%) tumors were overrepresented. The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%. Immunohistochemical loss of the corresponding MMR protein was demonstrated in 33/36 (92%) tumors analyzed.

CONCLUSION: The combined data from our cohorts demonstrate that ovarian cancer associated with Lynch syndrome typically presents at young age as early-stage, non-serous tumors, which implicates that a family history of colorectal and endometrial cancer should be specifically considered in such cases.

abstract: Tubal ligation and the risk of ovarian cancer: review and meta-analysis — Hum Reprod Update (serous/mucinous/endometrioid)

BACKGROUND The reduction of ovarian cancer (OC) risk in women with a history of tubal ligation (TL) has been reported repeatedly, mostly on small populations. We have aimed to provide a critical overview of the studies available to date and to conduct a meta-analysis.

METHODS There were 40 relevant studies identified. The studies were divided into two groups for strict and extended meta-analysis, respectively. Subgroup analysis was performed for age, time dependency since TL, histological types of OC and BReast CAncer (BRCA) mutation.

RESULTS Meta-analysis of 13 strictly selected studies showed a reduced risk of epithelial OC by 34%. The protective effect of TL was confirmed even in a subgroup of women 10–14 years after the procedure. The risk reduction was confirmed for the endometrioid (RR = 0.40) and serous (RR = 0.73) cancers but not for mucinous.

CONCLUSIONS The review of relevant articles, as well as the meta-analysis of selected studies, yields consistent data on a significant reduction of OC risk in women who had undergone TL. The results of this meta-analysis should provide an impulse for further research on the etiology of ovarian epithelial cancers, focusing particularly on the importance of retrograde transport of endometrial cells.

Endometrioid ovarian carcinoma benefits from aromatase inhibitors: case report and literature review (abstract) Dr Yi Pan (author)

(case report/review) Conclusions Endometrioid ovarian carcinoma may benefit from aromatase inhibitors, especially when the tumour burden is low after primary chemotherapy or when the inhibitor is used as maintenance therapy between chemotherapies.