title: Distinct molecular landscapes between endometrioid and nonendometrioid uterine carcinomas.
abstract: 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.
authors.affiliation: Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, New York, NY.
authors.forename: Nathaniel L
authors.identifier: 0000-0002-3871-4282
authors.initials: NL
authors.lastname: Jones
authors.affiliation: Caris Life Sciences, New York, NY.
authors.forename: Joanne
authors.initials: J
authors.lastname: Xiu
authors.affiliation: Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, New York, NY.
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Chatterjee-Paer
authors.affiliation: Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, New York, NY.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Buckley de Meritens
authors.affiliation: Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, New York, NY.
authors.forename: William M
authors.initials: WM
authors.lastname: Burke
authors.affiliation: Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, New York, NY.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Tergas
authors.affiliation: Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, New York, NY.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Wright
authors.affiliation: Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, New York, NY.
authors.forename: June Y
authors.initials: JY
authors.lastname: Hou
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000737:chemistry / Q000473:pathology / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000737:chemistry / Q000473:pathology / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018269:Carcinoma, Endometrioid / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000473:pathology / Q000556:secondary; D002296:Carcinosarcoma / Q000737:chemistry / Q000473:pathology / Q000556:secondary; D004260:DNA Repair / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D016889:Endometrial Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins
keywords: genomic profiling; molecular targets; uterine cancer; uterine carcinosarcoma; uterine serous carcinoma