[1047] 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.

Correlation between molecular abnormality, consensus diagnosis, IHC for p53 and p16 and clinical outcomes

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
AKT (1)	Endometrioid	0	0
No mutations detected (11)	6 serous, 5 endometrioid, 1 no consensus	6 of 11 (3 DOD)	3 of 11

Of the 13 cases with a consensus diagnosis of endometrioid ca, RAS mutations were noted in 6. 3 of these tumors also showed p53 OE and 2 of these patients died of disease (DOD). Of 8 cases with a consensus diagnosis of serous carcinoma, PIK3CA mutations were noted in 3; 2 with exon 9 mutations also showed p53 OE. The prognosis is difficult to assess due to small numbers and patients lost to follow up (LFU).
Conclusions: A consensus diagnosis of endometrioid carcinoma correlates with presence of RAS mutations, and p53 OE in these cases correlated with worse clinical outcomes. PIK3CA mutations were present in tumors with serous and endometrioid morphology, concurrent p53 OE was seen in cases with PIK3CA exon 9 mutations, but not exon 20 mutations. The impact of PIK3CA mutations on clinical outcome cannot be determined due to small numbers. PIK3CA and RAS mutations can co-exist in ECs.
Category: Gynecologic & Obstetrics

Wednesday, March 2, 2011 1:00 PM

Poster Session VI # 171, Wednesday Afternoon