Molecular Alterations in Morphologically Ambiguous Endometrial Carcinomas.
Karuna Garg, Douglas A Levine, Bogomolniy Faina, Wethington Stephanie, Robert A Soslow. MSKCC, New York
Background: Endometrial carcinomas (ECs) are divided into type 1 and type 2 cancers. Type 1 tumors are low grade endometrioid carcinomas with good clinical outcomes, associated with microsatellite instability and mutations in PTEN, K-RAS and CTNNB1. Type 2 tumors are aggressive, high grade ECs that often show p53 mutations. Both type 1 and type 2 ECs can have PIK3CA mutations, that can coexist with mutations in PTEN and p53. We have previously studied a group of morphologically ambiguous ECs with overlapping features of type 1 and 2 tumors, for interobserver diagnostic concordance and IHC for p53 and p16, and found that p53 overexpression (OE) correlates with adverse clinical outcomes. In this study, we wanted to assess the molecular abnormalities of these ECs and whether they had a prognostic impact.
Design: Twenty three ECs (n=23) with ambiguous morphology that had been stained for p53 and p16 formed the study group. These tumors were subjected to sequenom analysis for hotspot mutations in PIK3CA, KRAS, NRAS, and AKT. Sequencing results for PIK3R1 and PTEN are forthcoming.
Results: Of the 23 cases, mutations were detected in 12 (52%). Correlation between mutation status, morphologic impression and IHC for p53 and p16 are shown in table 1.
|Mutation analysis (number of cases)||Consensus diagnosis||p53 OE||p16 OE|
|RAS mutations||endometrioid||3 of 6 (2 DOD)||0 of 6|
|PIK3CA exon 9 (2)||Serous||2 of 2 (1 DOD)||1 of 2|
|PIK3CA exon 20 (2)||1 serous, 1 endometrioid||0 of 2 (LFU)||1 of 2|
|RAS/AKT/PIK3CA (1)||No consensus diagnosis||0||0|
|No mutations detected (11)||6 serous, 5 endometrioid, 1 no consensus||6 of 11 (3 DOD)||3 of 11|