paywalled: MR Imaging of Malignancies Arising in Endometriomas and Extraovarian Endometriosis

MR Imaging of Malignancies Arising in Endometr... [Radiographics. 2012] - PubMed - NCBI

Radiographics. 2012 May

Abstract: 

Cancers that arise in ovarian or extraovarian endometriosis are a distinct disease category with a histologic profile different from that of the more common epithelial ovarian cancers and with a better prognosis.

Because the malignant transformation of endometriomas is rarely associated with lymphadenopathy or peritoneal carcinomatosis, a high index of suspicion on the part of the radiologist is necessary to establish a timely diagnosis of endometriosis-related ovarian cancers and allow appropriate oncologic management. Although imaging is not currently performed for surveillance of endometriosis, magnetic resonance (MR) imaging is often performed when surgical treatment is under consideration................. For definitive diagnosis, histopathologic analysis is required.

paywalled - Unravelling the two entities of endometrioid ovarian cancer: A single center clinical experience

Unravelling the two entities of endometrioid ovarian cancer: A single center clinical experience

Purchase

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Abstract

Objective

Due to the increasing prevalence of the benign condition, ovarian carcinoma arising from endometriosis is emerging as a relevant clinical entity with an unclear biological signature. We have investigated clinical and histologic features of endometriosis-associated endometrioid ovarian cancer using an institutional retrospective database.

Methods

Patients diagnosed with endometrioid ovarian cancer at our institution were divided into two groups according to the fulfillment or not of Sampson's and Scott's criteria for the detection of endometriosis-associated ovarian cancer. Clinical and histological data were reported and compared. Survival analysis was obtained using the log-rank test in an unadjusted Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards regression model to establish independent factors associated with endometriosis-associated endometrioid ovarian cancer and to identify predictors of survival.

Results

Patients with endometriosis-associated endometrioid ovarian cancer were significantly younger, had a lower disease stage (77% vs 38%; p = 0.003), a less prevalent high grade tumor (38% vs 82%; p = 0.002) and a higher prevalence of squamous and mucinous metaplasia. 

The rate of endometrial cancer diagnosis was significantly higher in women with endometriosis-associated endometrioid ovarian cancer (33%) than in other patients (11%) (p = 0.04) with a 92% concordance between ovarian and endometrial histologic tumor grade. A significant difference in survival rate could not be demonstrated between patients with or without endometriosis.

Conclusions

The analysis of a retrospective endometrioid ovarian cancer database may allow to suggest a molecular, morphological and clinical parallelism between endometrial and endometrioid ovarian cancer.

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Highlights

► Endometriosis-associated endometrioid ovarian tumors possess a different biologic signature when compared to cancers not associated with the disease.
► Clinical course and molecular alterations of type I and type II endometrial tumors are similar to those detected respectively in endometriosis-associated and non-associated endometrioid ovarian tumor.

Endometriosis and ovarian cancer – Authors' reply : The Lancet Oncology

Endometriosis and ovarian cancer – Authors' reply : The Lancet Oncology

"Both Vercellini and colleagues and Guo and colleagues raise concerns about screening, with which we agree. Our findings should not suggest to clinicians or the public that screening for ovarian cancer should be implemented for women with endometriosis. Rather, we hope that our work stimulates further research that can refine risk groups related to endometriosis on the basis of anatomical site, epidemiological risk factors, or molecular features. Vercellini and colleagues raise an interesting point about atypical endometriosis, but this diagnosis is not standardised or commonly used and can not be addressed in epidemiological studies.

..................Regardless, the attenuated associations remain statistically significant.

(another) commentary: Endometriosis and ovarian cancer : The Lancet Oncology

Endometriosis and ovarian cancer : The Lancet Oncology

correspondence: Endometriosis and ovarian cancer : The Lancet Oncology

Endometriosis and ovarian cancer : The Lancet Oncology

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: Widespread endometriosis mimicking ovarian malignancy: A case report

Widespread endometriosis mimicking ovarian malignancy: A case report.

Abstract

A 26 year old Nigerian nulliparous woman who presented in the medical emergency unit of a teaching hospital was referred after two weeks of management to the gynecology casualty with a diagnosis of malignant left ovarian cyst, because of the ascites, massive haemorrhagic pleural effusion, a left ovarian mass and an elevated C-125 marker.

However, exploratory laparotomy, cytologic and histological examination of the pleural fluid and biopsied specimens revealed endometriosis. We present a case of intra and extra-pelvic endometriosis which simulated a malignant ovarian lesion and was histologically confirmed by cytology of the haemorrhagic pleural effusion and biopsy of the ovarian mass and peritoneal deposits obtained at laparotomy.

This is to draw the attention of clinicians to endometriosis as a cause of pleural effusion, ascites and groin swelling which can simulate ovarian cancer.

Behind the Headlines - Can endometriosis guide cancer tests? | GPonline.com

abstract: Different Levels of Sialyl-Tn Antigen Expressed on MUC16 in Patients With Endometriosis and Ovarian Cancer

Different Levels of Sialyl-Tn Antigen Expressed on MUC16 in Patients With Endometriosis and Ovarian Cancer

Abstract:

Objective:
Although CA125 antigen is a useful marker for ovarian cancer, its expression is also elevated in endometriosis. The purpose of this study was to develop an assay method for evaluating differentially glycosylated MUC16 (CA125 core protein) in patients with endometriosis and ovarian cancer.

Materials and Methods:
We prepared MUC16-enriched fractions from peritoneal fluid of patients with endometriosis and conditioned medium of ovarian carcinoma-3 cells by gel filtration, and evaluated the expression of sialyl-Lea, Tn, and sialyl-Tn antigens by dot blot analysis. A sandwich enzyme-linked immunosorbent assay was developed to measure the level of sialyl-Tn antigen expressed on MUC16 (sTn/MUC16). The level of sTn/MUC16 was compared between patients with endometriosis (n = 21) and ovarian cancer (n = 36) and in ovarian cancers with different clinical diagnostic criteria. Furthermore, distribution of MUC16 and sialyl-Tn antigen in ovarian cancer tissues was observed immunohistochemically.

Results:
Sialyl-Tn antigen was markedly detectable in the MUC16-enriched fractions from conditioned medium of ovarian carcinoma-3 cells but negligible in those from the peritoneal fluid of the patients with endometriosis. The level of sTn/MUC16 determined by a sandwich enzyme-linked immunosorbent assay was significantly higher in the patients with ovarian cancer than that in the patients with endometriosis (P < 0.001).
An elevated level of sTn/MUC16 was detected in 44% of the patients with ovarian cancer but not all the patients with endometriosis. This level increased more prominently in the patients with ovarian cancer than that of MUC16 as both the clinical stage and cytological grade advanced. An elevated level of sTn/MUC16 was frequently found in the patients with serous and endometrioid carcinomas. Consistent with this, sialyl-Tn antigen was colocalized with MUC16 in serous and endometrioid ovarian cancer tissues.

Conclusions:
Estimation of the sTn/MUC16 level may be useful for discriminating endometriosis from ovarian cancer and for evaluating the clinical stage, cytological grade, and histological type of ovarian cancer.

podcast: The Lancet Oncology : the association between endometriosis and ovarian cancer - interview with researcher

Feb 22: the association between endometriosis and ovarian cancer

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.

Gynecologic Oncology : The association between endometriosis and ovarian cancer: A review of histological, genetic and molecular alterations

.... PTEN play a part in the malignant transformation of endometriosis, some studies have revealed TP53 mutations in endometriotic lesions, and mutation of ARID1A (clear cell)

Highlights
► Atypical endometriosis is a transition from benign endometriosis to carcinoma.
► Endometriosis is characterized by genetic instability.
► Oxidative stress, inflammation and hyperestrogenism link endometriosis with cancer.

Preneoplasias of ovarian carcinoma : Biological and clinical aspects of different pathways of tumorigenesis

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

(full free pdf file access) Endometriosis-Associated Ovarian Carcinomas — NEJM

Prognostic analysis of ovarian cancer associated with endometriosis - abstract

Making strides in ovarian cancer research « BC Cancer Foundation's Blog - re: clear cell ovarian cancer/endometriosis

"We were able to show that ARID1A mutated in close to 50 per cent of clear cell carcinomas of the ovary and in a slightly fewer number of the related endometrioid carcinomas.
When we studied in detail two cases where there was endometriosis attached to the tumour, we found that the mutation was present even before the cells in endometriosis looked like cancer cells. This suggests that ARID1A mutations are a very early event and likely critical to the transformation of a non-cancerous disease into cancer.
We are fully confident that this discovery marks the start of finding real treatments for clear cell carcinoma – but there is still a lot of work to do in the future...."

Endometriosis related to family history of malignancies in the Yale series

Conclusions:
"These data suggest a familial association of endometriosis with ovarian, colon and prostate cancers. This evidence could support the genetics and molecular similarities between endometriosis javascript:void(0)and cancer. Future studies will be important to determine a clear genetic link between endometriosis and cancer."

Clinical Presentation of Endometrioid Epithelial Ovarian Cancer with Concurrent Endometriosis: A Multicenter Retrospective Study