Ovarian Cancer Biomarkers: Immunohistochemical Surrogates for Molecular Alterations

Outstanding advances over the last two decades have revolutionized ovarian cancer knowledge and therapy, moving toward a more personalized molecular targeted treatment. Once considered and treated as a single disease, ovarian cancer has through time demonstrated an intriguing heterogeneity that has been progressively unraveled in a multitude of distinct entities. Specifically, the recent WHO classification recognizes five main ovarian carcinoma histotypes that include high-grade serous, low-grade serous, mucinous, endometrioid, and clear cell carcinoma. So, every histotype is characterized not only by peculiar morphological features, but also by specific precursor lesions, pathogenesis, immunophenotype, molecular alterations, clinical behavior, and prognosis. Importantly, the development of molecular-targeted anticancer drugs has opened novel opportunities also for ovarian cancer treatment, implementing the oncological arsenal and significantly improving patient prognosis, especially when harboring targetable tumor molecular alterations. Indeed, patients with BRCA mutated high-grade serous carcinoma benefit from PARP inhibitors in maintenance therapy, whereas mismatch repair deficient and microsatellite instable endometrioid and clear cell carcinomas could take advantage from immunotherapy. Moreover, some molecular aberrations impact the clinical behavior of ovarian cancers, and the patient prognosis. In this context, an accurate pathological diagnosis with determination of clinically relevant molecular alterations is pivotal. Although molecular analyses are generally more accurate, standardized immunohistochemistry could satisfactorily surrogate some of them and be used easily and cost-effectively as the first testing approach in routine practice, avoiding unnecessary costly and distressful analyses. In this chapter, we delineate the routine immunohistochemical markers used as surrogates for the most relevant molecular alterations occurring in ovarian carcinoma.