[1090] PTEN Immunohistochemistry in Endometrial Carcinomas: Correlation with Mutation Analysis

K Garg, R Soslow, C Aghajanian, SU2C MSKCC Team, D Levine. Memorial Sloan Kettering Cancer Center, New York

Background: With evolving knowledge about molecular pathways involved in endometrial carcinogenesis, new drugs, including mTOR inhibitors and PI3K inhibitors, are being explored as potential therapeutic targets in endometrial carcinomas (EC). Biomarker development that could predict response to such therapeutic agents is important. PTEN is frequently inactivated in ECs, but antibodies for PTEN IHC have been difficult to work with and have shown variable results. Our aim was to assess PTEN mutation and IHC status in different types of ECs.
Design: Only ECs that had both PTEN IHC and mutational analysis data were included in this study. PTEN IHC was performed using monoclonal PTEN antibody from DAKO (clone 6H2.1). PTEN staining was assessed in nuclei and cytoplasm. Complete absence of staining in tumor cells in the presence of internal positive control (stromal cells, lymphocytes) was interpreted as PTEN loss. Cases with any staining were interpreted as PTEN positive. PTEN mutational analysis was performed.
Results: 29 ECs with PTEN IHC and mutation analysis were included in this study. Of the 15 FIGO grade 1-2 endometrial endometrioid carcinomas (EECs), 8 showed PTEN loss by IHC and PTEN mutations were noted in 4 cases (of these 4, 3 showed PTEN IHC loss while 1 case had positive PTEN IHC). Of the 4 FIGO grade 3 EECs, 3 showed PTEN IHC loss, and all 3 of these tumors showed PTEN mutations. Of the 9 type 2 carcinomas (8 serous and 1 carcinosarcoma), 3 showed IHC loss and none showed mutations in PTEN. One EC with endometrioid and undifferentiated components showed IHC loss and PTEN mutation. Loss of PTEN by IHC did not correlate with the presence of PTEN mutations. Cases with retained PTEN IHC almost always lacked PTEN mutations.

PTEN IHC and mutation analysis
FIGO 1-2 EEC (15)FIGO 3 EEC (4)SEROUS/MMMT (9)UNDIFFERENTIATED (1)
IHC PTEN loss8331
PTEN mutation (IHC status on cases with mutation)4 (3 IHC loss, 1 IHC positive)3 (3 with IHC loss)01 (1 with IHC loss)
EEC: endometrial endometrioid carcinoma, MMMT: carcinosarcoma


Conclusions: PTEN mutations appear to be a common event in type 1 ECs, none of the type 2 ECs showed PTEN mutations. There is lack of correlation between PTEN IHC and mutation analysis. Some ECs with PTEN loss by IHC do not have detectable mutations while presence of PTEN IHC staining usually correlates with absence of mutations. PTEN IHC loss in cases without mutations may be due to epigenetic changes such as methylation, these mechanisms of PTEN inactivation should be explored further.
Category: Gynecologic & Obstetrics

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 129, Wednesday Morning

 

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