TMEPAI Gene Amplification in Triple Negative Breast Cancers
N Samarnthai, P Saikumar, P Singha, MA Ventkatachalam, SR Gunn, I Yeh. University of Texas Health Science Center at San Antonio, San Antonio, TX
Background: Transmembrane, prostate androgen induced protein(TMEPAI), an androgen-induced, cell-cycle-regulated protein that is encoded by the TMEPAI gene on chromosome 20, has demonstrated overexpression in many cancers including breast. TMEPAI may play a significant role in tumorigenesis by preventing apoptosis and promoting invasiveness or migration of breast cancer cells. Only a few human breast cancers have been examined for TMEPAI, and this study was undertaken to look at the incidence of TMEPAI gene amplification in human breast cancer, particularly in triple negative cancers (ER-, PR-, HER2-).
Design: Fresh frozen tissues from 97 cases of breast cancer, including 85 invasive ductal carcinomas, 11 invasive lobular carcinomas and 1 mixed ductal and lobular carcinoma, were assayed by Agilent (Santa Clara, CA, USA) human genome CGH microarray 105A. Analysis was performed using Agilent (Santa Clara, CA, USA) genomic workbench 5.0 software. The locus chr20:55,656,858-55,719,947 for TMEPAI was visualized in each of the 97 breast cancer cases and degree of expression was noted as loss (-0.2 to <-0.7), normal (< 0.2 to >-0.2), gain (0.2 to < 0.5), or high copy gain (> 0.5). The TMEPAI findings were then correlated with histologic grade (Nottingham score) and breast prognostic markers as measured by immunohistochemistry and in situ hybridization, including ER, PR and HER2.
Results: 47/97 breast cancers (48.5%), including 45/85(53%) invasive ductal carcinomas and 2/11(18%) invasive lobular carcinomas, showed either gain (26/97, 26.8%) or high copy gain (21/97, 21.6%) of TMEPAI. The majority of the tumors with copy number gain were histologic grade 3 (34/47, 72.3%). Of the breast cancers with gains or high copy number gain, 25 were ER-negative (53.2%), 31 PR-negative (66%), and 36 HER2-negative (76.6%). In all, 18 of 31 triple negative cancers showed gene amplification of TMEPAI in our group of breast cancer cases (58.1%).