Somatic Deletions of the PolyA Tract in the 3′ Untranslated Region of Epidermal Growth Factor Receptor Are Common in Microsatellite Instability-High Endometrial and Colorectal Carcinomas

Context.-Epidermal growth factor receptor (EGFR) is overexpressed in up to 80% of colorectal and endometrial carcinomas. Deletions of the polyA tract in the 3' untranslated region (3' UTR) have been reported in microsatellite instability-high (MSI-H) colonic carcinomas, but their impacts on EGFR expression and downstream pathways are unclear. This phenomenon has not been reported in other MSI-H tumors. Objective.-To assess the 3' UTR polyA tract of EGFR in both endometrial and colorectal carcinomas and the mutational status of EGFR downstream pathways. Design.-Ninety-eight colorectal carcinomas and 47 endometrial carcinomas were included. EGFR 3' UTR polyA status was detected by capillary electrophoresis and Sanger sequencing. EGFR gene expression, EGFR copy numbers, and KRAS and BRAF mutation status were analyzed accordingly. Results.-The 3' UTR polyA tract was deleted in 18 of 23 (78%) MSI-H versus 0 of 24 microsatellite-stable endometrial carcinomas (P < .001). Similar observations were seen in colorectal carcinomas, in which 29 of 36 (81%) MSI-H, 1 of 62 (1.6%) microsatellite instability-low, and none of the microsatellite-stable tumors harbored the deletion (P < .001). A moderate increase in EGFR mRNA level was observed in endometrial carcinomas with 3' UTR polyA deletions versus those with wild-type polyA tract. Amplification of the EGFR gene was not observed. Deletions in polyA tract do not seem to affect the frequency of KRAS and BRAF mutations. Conclusions.-Deletions of EGFR 3' UTR polyA are frequent in endometrial and colorectal carcinomas, are confined almost exclusively to MSI-H tumors, and do not affect KRAS and BRAF mutations. (Arch Pathol Lab Med. 2012;136:510-516; doi: 10.5858/arpa.2010-0638-OA)