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Distinct molecular landscapes between endometrioid and nonendometrioid uterine carcinomas
Author(s) -
Jones Nathaniel L.,
Xiu Joanne,
ChatterjeePaer Sudeshna,
Buckley de Meritens Alexandre,
Burke William M.,
Tergas Ana I.,
Wright Jason D.,
Hou June Y.
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30537
Subject(s) - kras , serous fluid , clear cell , mucinous carcinoma , pathology , pten , cancer research , immunohistochemistry , carcinosarcoma , cancer , biology , medicine , carcinoma , adenocarcinoma , oncology , pi3k/akt/mtor pathway , colorectal cancer , genetics , apoptosis
Endometrial carcinoma (EC) is traditionally characterized as endometrioid and nonendometrioid based on histopathologic phenotypes. Molecular‐based classifications have been proposed, but are not widely implemented. Herein we examine molecular profiles between EC histologic subtypes. 3133 ECs were submitted between March 2011 and July 2014: 1634 Type I and 1226 Type II. In situ hybridization and immunohistochemistry were used to assess copy number and protein expression of selected genes. Sequenced variants in 47 genes were analyzed using the Illumina TruSeq Amplicon Cancer Panel. Type II EC included 628 cases of uterine serous cancer (USC), 136 cases of clear cell (CC), 361 cases of carcinosarcoma (CS), 38 cases of mucinous, and 36 cases of squamous cell. PI3K/Akt/mTOR pathway was most frequently dysregulated within Type I and mucinous histologies, least altered in CS and squamous. PD‐L1 expression was highest in mucinous, absent in squamous. ER/PR expression was common in Type II, most frequent in USC, mucinous, and squamous. Receptor tyrosine kinase was frequently dysregulated in Type II disease: HER2 amplification highest in USC and CC, EGFR mutations exclusively seen in mucinous EC, KRAS mutations common in mucinous, squamous, and Type I, and c‐MET overexpression high in CC and mucinous. BRCA1 and BRCA2 were most frequently mutated in CS. Grade 3 EC shares features of G1 tumor and Type II disease, most notably resembling CS. Endometrial carcinomas are a molecularly heterogeneous group of tumors. A histology‐based molecular map can identify rational targets to optimize treatment and guide future clinical trials.