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Targeted mutation analysis of endometrial clear cell carcinoma
Author(s) -
Hoang Lien N,
McConechy Melissa K,
Meng Bo,
McIntyre John B,
Ewanowich Carol,
Gilks Cyril Blake,
Huntsman David G,
Köbel Martin,
Lee ChengHan
Publication year - 2015
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12581
Subject(s) - pten , serous fluid , carcinoma , endometrial cancer , serous carcinoma , cancer research , biology , clear cell , clear cell carcinoma , arid1a , mutation , carcinogenesis , endometrium , pathology , oncology , gene , cancer , medicine , genetics , pi3k/akt/mtor pathway , ovarian cancer , endocrinology , apoptosis
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 .