**6.3 Molecular pathology ovarian clear cell carcinomas**

The genomic aberrations found in OCCCs involve *PIK3CA* activating mutations (40–50%), *ARID1A* loss of function mutations (50–75%), *MET* gene amplifications, mutations in *ARID1B* (10%), *KRAS* (15%), *PPP2R1A* (15%), *TERT* promoter (15%), *SMARCA4*, *PTEN* (1–5%), *PIK3CA, PIK3R1, AKT2, TP53* (5–20%) and *ZNF217*

*Recent Advances in Classification and Histopathological Diagnosis of Ovarian Epithelial… DOI: http://dx.doi.org/10.5772/intechopen.106545*

transcription factor overexpression, which is associated with poor outcome [128, 129]. *PIK3CA* mutations commonly coexist with *ARID1A* genomic alterations and are more frequent in endometriosis-associated OCCCs [128]. Studies on genes involved in antioxidant cell machineries such as *GPX3* (glutathione peroxidase 3), *GLRX3* (glutaredoxin) and *SOD3* (superoxide dismutase) have shown that these genes are highly expressed in CCOCs resulting in tumour chemotherapy resistance [129, 130]. *HER2* gene amplification (15%) and Mismatch Repair (MMR) gene deficiency (2–3%) have also been identified [131]. MMR germline mutations can be found in 10% of OCCCs and may predispose them in developing OCCCs [131]. Therefore, MMR gene expression should be tested by immunohistochemical methods or by MSI testing in order to identify OCCCs associated with MMR deficiency and/or Lynch syndrome. This is important, taking into account that MMR deficient OCCCs are correlated with favourable clinical outcome even in advanced stages [132]. Mutations of the *TP53* gene are usually rare, albeit abnormal p53 expression (7%) has been reported and is associated with adverse prognosis [132]. Molecules involved in the PIK3/AKT/mTOR pathway and loss of function of *ARID1A* gene might be targeted therapeutically by using mTOR inhibitors and through inhibition of EZH2 transcription factor, respectively [133].
