Lynch Syndrome Essay

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ROLE OF IMMUNOHISTOCHEMISTRY IN THE DIAGNOSIS OF SYNDROMIC GYNECOLOGICAL CANCERS
Both ovarian and endometrial carcinomas can be expression of genetically inherited syndromes.
Two main hereditary cancer syndromes are known that predispose to cancers occurring in the gynecological tract, namely Lynch and hereditary Breast and Ovary Cancer syndromes.
Lynch syndrome is due to germline mutations in the MMR system, including MLH1, MSH2, MSH6 and PMS2 genes, and in EPCAM gene, that cause high microsatellite instability and increase the risk of endometrioid, clear cell and undifferentiated carcinoma. Lynch syndrome is responsible of 5% of endometrial cancers and 1% of ovarian cancer cases, but high microsatellite instability is found in 30-40% of endometrial carcinomas, due to somatic mutations and MSH1 promoter methylation. The pathologist plays a fundamental role in identifying cancers harboring high microsatellite instability. In fact, there are histological clues suggesting Lynch syndrome: prominent peritumoral lymphocytes, increased lymphocytes (>42 per 10 high-power fields) located within the boundary of tumor cell nests or glands, and tumor heterogeneity, defined as juxtaposed
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Conclusion
This short review intended to provide an updated overview of the essential IHC markers currently used in diagnostics of gynecologic diseases along with their molecular rationale. Over the last decade, there have been unpredictable advances on the understanding of the molecular pathogenesis of gynecologic malignancies. It is advisable that this knowledge will be the foundation for a molecularly-oriented therapeutic approach to improve the outcome and reduce the side effects of patients with gynecological

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