Targeted mutation analysis of endometrial clear cell carcinoma. Issue 5 (13th January 2015)

• Record Type: Journal Article
• Authors: Hoang, Lien N; McConechy, Melissa K; Meng, Bo; McIntyre, John B; Ewanowich, Carol; Gilks, Cyril Blake; Huntsman, David G; Köbel, Martin; Lee, Cheng‐Han
• Is Part Of: Histopathology. Volume 66:Issue 5(2015)
• Page Start: 664
• Page End: 674
• Publication Date: 2015-01-13
• Subjects: Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.12581
• Languages: English
• ISSNs: 0309-0167

Abstract

<abstract abstract-type="main" id="his12581-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="his12581-sec-0001" sec-type="section"> <title>Aims</title> <p>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.</p> </sec> <sec id="his12581-sec-0002" sec-type="section"> <title>Methods and results</title> <p>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 (HNF1β<sup>+</sup>) and oestrogen receptor<sup>−</sup>] 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 <italic>TP53</italic> and <italic>PPP2R1A</italic> mutations, without <italic>PTEN</italic>, <italic> CTNNB1</italic> or <italic>ARID1A</italic> mutation). No mutations in <italic>PTEN</italic>, <italic> CTNNB1</italic> or <italic>POLE</italic> were identified.</p> </sec> <sec id="his12581-sec-0003" sec-type="section"> <title>Conclusions</title> <p>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 <italic>TP53</italic>‐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.</p> </sec> </abstract>