Is there a relationship in-between ovarian endometriosis and ovarian cancer? Immunohistochemical profile of four cases with coexisting ovarian endometriosis and cancer

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Abstract

Endometriosis (EMs) is a benign disease characterized by the presence of endometrial tissue outside the uterine cavity. EMs associated with ovarian cancer (OC) has a relative low incidence (5% to 10%), sometimes with evidence of a transition stage through atypical EMs (1.6% cases). We have assessed 135 consecutive patients with either EMs or OC and, out of them, our study reports on four cases of ovarian EMs and OC: two cases with endometrioid OC and two cases with high-grade serous OC (HGSOC). Cases with EMs and HGSOC are extremely rarely reported in the literature – we could find not more than 30 cases. The main objective of our research was to observe the possible similarities between EMs and OC. Secondly, we analyzed the differences between EMs associated with endometrioid OC and EMs associated with HGSOC. We evaluated them in terms of clinical status (age, stages of EMs and OC) and immunohistochemical (IHC) expression of estrogen receptor (ER), progesterone receptor (PR), Ki67, p53, p16, Wilms’ tumor 1 (WT1), cluster of differentiation (CD) 34 and CD10 immunomarkers – we could not find in the literature all these markers assessed, in the same time, to such samples. Our results indicated that there are no similarities between EMs and OC and no atypical EMs was identified in our cases. We recorded higher values of ER expression in EMs associated with HGSOC than in EMs associated with endometrioid OC. Higher values of ER expression were also recorded in OC than in endometriotic foci. There were no differences in proliferative rate of endometriotic foci associated with endometrioid OC, compared to EMs associated with HGSOC. An aberrant IHC expression for p53 protein and p16 protein was noted only in HGSOC. Also, a positive immunostaining for Wilms’ tumor 1 (WT1) was identified only in HGSOC. Higher values of microvessel density were recorded in OC but not in endometriotic foci. We concluded that there were no similarities between EMs and OC for the cases included in our study, but we noticed differences in terms of Ki67 index and also between hormonal receptors expression in EMs associated with HGSOC, comparing with EMs associated with endometrioid OCs. These results may represent a “brick” for future researches on the less understood EMs associated with type II of OCs, especially with HGSOC. Identifying the best marker, which can predict the risk of developing OC for the patients with EMs, may lead to discover new specific therapeutic agents and, therefore, a better, tailored, therapy.

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Most cited references 60

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Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies.

K S McCarty, L S Miller, E B Cox … (1985)

Attempts at histochemical localization of estrogen receptor with anti-steroid antibody or some fluoresceinated estrogens have given unacceptable sensitivities and specificities when compared with biochemical methods or clinical response. In the present study a monoclonal antibody against estrogen receptor (H222 Sp gamma) was used on cryostat sections of freshly frozen breast tumors with a peroxidase-antiperoxidase immunoperoxidase technique. Biochemical receptor analyses were by dextran-coated charcoal analyses. Tumors from three separate cohorts of patients were studied as follows: population A, 62 primary breast cancers from 1983; population B, 72 primary lesions stored from 1976 to 1983; and population C, 23 patients with metastases, treated with hormonal therapy. Distinct staining was seen in the cell nucleus. A semiquantitative relationship was seen between histochemical score assessment of staining and biochemical assay in each cohort. The sensitivity and specificity using a threshold of 75 for the histochemical score and more than 20 femtomoles/mg of protein for dextran-coated charcoal analyses were as follows: population A, specificity, 89%, and sensitivity, 95%; population B, specificity, 94%, and sensitivity 88%; and for population C, the comparison was with objective clinical response yielding specificity, 89%, and sensitivity, 93%.

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The Dualistic Model of Ovarian Carcinogenesis: Revisited, Revised, and Expanded.

Robert Kurman, Ie-Ming Shih (2016)

Since our proposal of a dualistic model of epithelial ovarian carcinogenesis more than a decade ago, a large number of molecular and histopathologic studies were published that have provided important insights into the origin and molecular pathogenesis of this disease. This has required that the original model be revised and expanded to incorporate these findings. The new model divides type I tumors into three groups: i) endometriosis-related tumors that include endometrioid, clear cell, and seromucinous carcinomas; ii) low-grade serous carcinomas; and iii) mucinous carcinomas and malignant Brenner tumors. As in the previous model, type II tumors are composed, for the most part, of high-grade serous carcinomas that can be further subdivided into morphologic and molecular subtypes. Type I tumors develop from benign extraovarian lesions that implant on the ovary and which can subsequently undergo malignant transformation, whereas many type II carcinomas develop from intraepithelial carcinomas in the fallopian tube and, as a result, disseminate as carcinomas that involve the ovary and extraovarian sites, which probably accounts for their clinically aggressive behavior. The new molecular genetic data, especially those derived from next-generation sequencing, further underline the heterogeneity of ovarian cancer and identify actionable mutations. The dualistic model highlights these differences between type I and type II tumors which, it can be argued, describe entirely different groups of diseases.

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Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study

Weiva Sieh, Martin Köbel, Teri Longacre … (2013)

Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival. 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study. Participants included in our analysis had been diagnosed with invasive serous, mucinous, endometrioid, or clear-cell carcinomas of the ovary. For a patient to be eligible, tissue microarrays, clinical follow-up data, age at diagnosis, and tumour grade and stage had to be available. Clinical data were obtained from medical records, cancer registries, death certificates, pathology reports, and review of histological slides. PR and ER statuses were assessed by central immunohistochemistry analysis done by masked pathologists. PR and ER staining was defined as negative (<1% tumour cell nuclei), weak (1 to <50%), or strong (≥50%). Associations with disease-specific survival were assessed. 2933 women with invasive epithelial ovarian cancer were included: 1742 with high-grade serous carcinoma, 110 with low-grade serous carcinoma, 207 with mucinous carcinoma, 484 with endometrioid carcinoma, and 390 with clear-cell carcinoma. PR expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001) and high-grade serous carcinoma (log-rank p=0·0006), and ER expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001). We recorded no significant associations for mucinous, clear-cell, or low-grade serous carcinoma. Positive hormone-receptor expression (weak or strong staining for PR or ER, or both) was associated with significantly improved disease-specific survival in endometrioid carcinoma compared with negative hormone-receptor expression, independent of study site, age, stage, and grade (hazard ratio 0·33, 95% CI 0·21-0·51; p<0·0001). Strong PR expression was independently associated with improved disease-specific survival in high-grade serous carcinoma (0·71, 0·55-0·91; p=0·0080), but weak PR expression was not (1·02, 0·89-1·18; p=0·74). PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to establish whether hormone-receptor status predicts response to endocrine treatment, and whether it could guide personalised treatment for ovarian cancer. Carraresi Foundation and others. Copyright © 2013 Elsevier Ltd. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): Rom J Morphol Embryol

Journal ID (iso-abbrev): Rom J Morphol Embryol

Journal ID (publisher-id): RJME

Title: Romanian Journal of Morphology and Embryology

Publisher: Academy of Medical Sciences, Romanian Academy Publishing House, Bucharest

ISSN (Print): 1220-0522

ISSN (Electronic): 2066-8279

Publication date (Print): Jan-Mar 2020

Publication date (Electronic): 07 July 2020

Volume: 61

Issue: 1

Pages: 157-165

Affiliations

[1 ]Department of Obstetrics and Gynecology, Doctoral School, Ovidius University of Constanţa, Romania

[2 ]PhD Student, Doctoral School, Ovidius University of Constanţa, Romania

[3 ]Department of Clinical Pharmacology, University of Medicine and Pharmacy of Craiova, Romania

[4 ]Department of Surgery, Doctoral School, Ovidius University of Constanţa, Romania

[5 ]Clinical Service of Pathology, Sf. Apostol Andrei Emergency County Hospital, Constanţa, Romania

[6 ]Department of Pathology, Faculty of Medicine, Ovidius University of Constanţa, Romania

[7 ]Department of Internal Medicine, University Regional Hospital, Constanţa, Romania; Department of Internal Medicine, Ovidius University of Constanţa, Romania

[8 ]Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology, Ovidius University of Constanţa, Romania

[9 ]Department of Obstetrics and Gynecology, University Regional Hospital, Craiova, Romania

[10 ]Department of Obstetrics and Gynecology, Ovidius University of Constanţa, Romania

Author notes

Corresponding Author: Irina Tica Associate Professor, MD, PhD, Department of Internal MedicineOvidius University of Constanţa Campus, 1 University Alley, Housing B900470 ConstanţaRomania+40724–834 864 irinatica@ 123456gmail.com

Article

Publisher ID: 610120157165

DOI: 10.47162/RJME.61.1.18

PMC ID: 7728120

PubMed ID: 32747907

SO-VID: ef0d5dc6-0c5b-46d3-b552-b1df105f1a7c

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This is an open-access article distributed under the terms of a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Public License, which permits unrestricted use, adaptation, distribution and reproduction in any medium, non-commercially, provided the new creations are licensed under identical terms as the original work and the original work is properly cited.

Is there a relationship in-between ovarian endometriosis and ovarian cancer? Immunohistochemical profile of four cases with coexisting ovarian endometriosis and cancer

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Karger: Oncology

Most cited references 60

Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies.

The Dualistic Model of Ovarian Carcinogenesis: Revisited, Revised, and Expanded.

Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study

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