Clinicopathological heterogeneity in ovarian clear cell adenocarcinoma: a study on individual therapy practice

Ovarian clear cell adenocarcinoma (CCA) has been believed to be a lethal histological subtype of an epithelial ovarian adenocarcinoma (EOA); its precursor has been assumed to be endometriosis. However, it has been reported that CCAs occasionally exhibit different clinical behaviors, suggesting that CCAs might not belong to a single category. We focused on CCAs combined with other histological types of EOAs; we re-evaluated the pathology of 46 CCAs and divided them into two subgroups: 35 CCAs alone (pure-type CCAs); and 11 CCAs with other histological types, endometrioid adenocarcinomas (EAs) or/and serous adenocarcinomas (SAs) (mixed-type CCAs). Immunohistochemical analysis for expression of ARID1A, p53, PTEN, Annexin 4, hepatocyte nuclear factor-1β (HNF-1β), and WT-1 was employed. We identified that patients with endometriosis were younger than those without endometriosis in pure-type CCAs (P < 0.005). In mixed-type CCAs, the immunohistochemical-staining patterns revealed internal transition of each histological component. In pure-type CCAs, expressions of ARID1A and p53 were mutually altered, and altered expression of p53 was associated with worse prognosis than that of ARID1A (P < 0.001). Our results provide evidence that CCAs would have clinicopathological heterogeneity, determining the patient's prognosis. Furthermore, immunohistochemical analysis may shed light on the selection of appropriate treatment, including chemotherapy.