Kanwal Zahra, Ahmareen Khalid, Ashok Kumar Tanwani.
Estrogen and Progesterone Receptor Expression in Epithelial Ovarian Cancers and Their Correlation with Histologic Subtypes, Grades and Immnuoexpression.
Int J Pathol Jan ;15(4):149-55.

Context: Ovarian cancer is the most fatal gynecological malignancy and its major burden is shared by Epithelial Ovarian Cancers (EOC). Total 85% of all ovarian cancers belonged to EOC. Despite knowing the involvement of Estrogen and Progesterone in their carcinogenesis, complete understanding of how they transform ovarian surface epithelium (OSE) is still unknown. Their associations with EOC may differ by different subtypes and grades which can be helpful in determining the hormonal need of each. This knowledge can also be valuable for targeted hormonal therapies comparable to those already established in carcinoma breast. Objective: To evaluate Estrogen and Progesterone receptor expression in various histologic subtypes and grades of Epithelial Ovarian Cancers. Materials and Methods: Total 82 cases of EOCs including both ovarian biopsies and surgical resections were collected, processed and stained. Hematoxylin and Eosin (H&E) stained slides were examined and histological sub typing of EOC was done. Both Serous and Non-Serous carcinomas were graded. Immunohistochemistry was performed on selected sections to evaluated ER, PR immunoexpression. Extent of immunostaining was noted and graded as 0 to 4+ on the basis of percentage of nuclear staining of tumor cells. Results: Total number of cases were 82 (n=82). Median age was 48 years. Most common histologic subtype was Serous carcinoma. The commonest grade among Serous carcinoma was high grade and maximum cases of Non- Serous carcinomas belonged to poorly differentiated (G3) category. ER immunoexpression was observed in 61% of total cases. Correlation of ER immunoexpression with various subtypes of EOC proved to be statistically significant with Endometrioid subtype showing maximum immunoreactivity. Among various grades low grade Serous carcinoma proved to be most immunoreactive for ER. PR expression was observed in 41.5% of cases with Serous carcinomas most immunoreactive for PR. Correlation of PR immunoexpression with grades of Serous carcinoma was statistically significant with maximum number of low grade Serous positive for PR. For combined ER/PR expression 38% cases were ER+/PR+, 22% were ER+/PR-, 4% were ER-/ PR+ and 36% were ER- / PR-. Correlation of ER/PR immunoexpression with total cases (n=82) was statistically significant, 64% of total cases showed immunoreactivity for either ER or PR. Correlation of ER/PR immunoexpression with histologic subtypes was also statistically significant with most ER+/PR+ cases belonged to Serous and Endometrioid subtypes while most cases of Mucinous and all cases of Clear cell and undifferentiated carcinomas belonged to ER-/PR- category. Conclusions: A variable expression of ER and PR was noted in EOC among different subtypes and grades. Most cases showed ER immunoexpression, its association with postmenopausal status, link to non-clear cell carcinomas and frequent relation with low grade tumors. These findings strengthen the hypothesis that low grade tumors require ER for tumor initiation and progression, high grade tumors are independent of sex steroids. In contrast to ER smaller number of EOC were positive for PR. They were associated with premenopausal status and low grades of Serous and Non-Serous carcinomas. These findings are consistent with the fact that epithelial malignancies are associated with decreased PR immunoexpression which is gradually lost as tumor progresses from low to high grade. Much lower immunoreactivity of both receptors for Mucinous tumors and absolutely no immunoreaction for Clear cell carcinoma favor the hypothesis that they are distinct morphological and epidemiological entities separate from non-clear cell carcinomas.

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