[1116] Molecular Changes in Endometrial Clear Cell Carcinomas and Carcinomas with Clear Cell Features

Deborah DeLair, Douglas Levine, Faina Bogomolniy, Stephanie Wethington, Guangming Han, Robert A Soslow. Memorial Sloan-Kettering Cancer Center, New York, NY; University of Calgary, Calgary, Canada

Background: Little is known about the molecular changes in endometrial clear cell carcinoma and endometrial carcinoma with clear cell changes. A group of 44 cases of endometrial carcinomas originally diagnosed as clear cell (CC), mixed clear cell (MEC), or carcinoma with clear cell changes were previously studied to evaluate diagnostic interobserver variability and immunoreactivities of the markers HNF-1β, p53, ER, and p16. Based on the consensus diagnoses of a panel of 5 gynecologic pathologists, the tumors were reclassified as CC, endometrioid (EC), serous (SC), undifferentiated (UD), carcinosarcoma (MMMT), or no consensus diagnosis (NCD). We sought to evaluate certain molecular changes in this group of tumors.
Design: Thirty-seven of these cases had adequate material for sequenom analysis for hotspot mutations in the genes PIK3CA, PIK3R1, KRAS, NRAS, and PTEN. These included 11 CC, 9 EC, 14 SC, 1 UD, 1 MMMT, and 1 NCD.
Results: Of the 37 studied cases, mutations were detected in 15 (41%) tumors. The results are shown in the table below as well as the corresponding immunophenotypes.

ConsensusMutation (s)HNF1-ßERp53p16Outcome
CCPIK3R1, PIK3CA, KRAS+---DOD
CCPIK3R1----DOD
CCKRAS----DOD
ECPIK3CA, KRAS, NRAS++--LTF
ECKRAS++--DOD
ECPIK3R1-+--DOD
ECPTEN-++-LTF
ECPIK3CA-+--DOD
ECPIK3R1, KRAS-+--DOD
SCPIK3CA-+--DOD
SCPIK3R1-+--NED
SCPIK3CA-+++AWD
SCPIK3R1-+-+LTF
SCPIK3CA-+-+NED
SCKRAS-++-DOD
DOD=Dead of disease, AWD=Alive with disease, NED=No evidence of disease LTF=Lost to follow-up

PIK3CA and PIK3R1 mutations occurred in all tumor types with detected mutations and 1 CC contained both. None of the CC with detected mutations showed overexpression of p53 by immunohistochemistry (IHC). A mutation in PTEN was detected in only 1 EC. KRAS mutations were also present in all tumor types and coexisted with both PIK3R1 and PIK3CA in 2 separate EC and alone in 1 EC and 1 SC. Overexpression of p53 by IHC occurred in tumors with mutations in PTEN, KRAS, PIK3R1, and PIK3CA. HNF-1ß was positive by IHC in tumors with PIK3CA, PIK3R1, KRAS, and NRAS mutations. No mutations were detected in 8 CC, 3 EC, 8 SC, 1 UD, 1 MMMT, and 1 NCD. Mutation status did not appear to correlate with clinical outcome.
Conclusions: Endometrial clear cell carcinomas and carcinomas with clear cell features are a heterogeneous group of tumors and show a spectrum of mutations and corresponding tumor types.
Category: Gynecologic & Obstetrics

Monday, March 19, 2012 9:15 AM

Platform Session: Section E, Monday Morning

 

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