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.
|FIGO 1-2 EEC (15)||FIGO 3 EEC (4)||SEROUS/MMMT (9)||UNDIFFERENTIATED (1)|
|IHC PTEN loss||8||3||3||1|
|PTEN mutation (IHC status on cases with mutation)||4 (3 IHC loss, 1 IHC positive)||3 (3 with IHC loss)||0||1 (1 with IHC loss)|