Targeted mutation analysis of endometrial clear cell carcinoma

Aims Endometrial clear cell carcinomas ( CCC ) constitute fewer than 5% of all carcinomas of the endometrium. Currently, little is known regarding the genetic basis of endometrial CCC . Methods and results We performed genomic and immunohistochemical analyses on 14 rigorously reviewed pure endometrial CCC . The genomic analysis consisted of sequencing the coding regions of 26 genes implicated previously in endometrial carcinoma. Twelve of 14 tumours displayed a prototypical CCC immunophenotype [napsin A +, hepatocyte nuclear factor‐1β ( HNF 1β + ) and oestrogen receptor − ] and all showed intact mismatch repair protein expression. We detected mutations in 11 of 14 tumours, and there was a predominance of mutations involving genes that are mutated more frequently in endometrial serous carcinomas than in endometrioid carcinomas. Two tumours displayed a prototypical serous carcinoma mutation profile (concurrent TP 53 and PPP 2 R 1 A mutations, without PTEN , CTNNB 1 or ARID 1 A mutation). No mutations in PTEN , CTNNB 1 or POLE were identified. Conclusions The overall mutation profile of this cohort of endometrial CCC appears to be more serous‐like than endometrioid‐like, with a minor subset in the TP 53 ‐mutated CCC showing serous carcinoma profile. These findings provide new insights into the molecular features of morphologically prototypical endometrial CCC , and underscore the need for further investigations into the oncogenesis of endometrial CCC .