Differences in TMPRSS2-ERG Gene Fusion, PTEN Deletion, and SPINK1 Overexpression in Prostate Cancer in African-American and Caucasian Men
Francesca Khani, Juan Miguel Mosquera, Kyung Park, Abhishek Srivastava, Ashutosh K Tewari, Mark A Rubin, Brian D Robinson. Weill Cornell Medical College, New York
Background: Prostate cancer (PCa) is known to exhibit differences among racial/ethnic groups, with African-Americans (AA) having a higher incidence and mortality from the disease than that observed in Caucasians (CAU). Although socioeconomic factors may contribute to these differences, underlying genetic differences are believed to play a role as well. In particular, TMPRSS2-ERG gene fusions, which are present in approximately 50% of PCa overall, have not been studied in large cohorts of AA patients. Similarly, while overexpression of SPINK1 and deletion of PTEN have been associated with more aggressive PCa, differential expression in patients of different ethnicities has yet to be characterized.
Design: A tissue microarray (TMA) was constructed containing tumor samples from 105 AA men who underwent radical prostatectomy (RP) at our institution. The control group was derived from a cohort of 112 PCa from CAU men treated by RP at the same institution. Clinical and pathologic characteristics of the two groups were similar. SPINK1 overexpression was evaluated by IHC using a monoclonal antibody. Any positive staining was considered overexpressed. TMPRSS2-ERG gene fusion and PTEN deletion were evaluated by FISH.
Results: TMPRSS2-ERG gene fusions were identified in 48/112 tumors (42.9%) in the control group of CAU men. In the AA cohort, however,TMPRSS2-ERG gene fusions were found in 28/105 tumors (26.7%; p<0.02). There was no significant difference in the mechanism of gene fusion between the two cohorts (translocation vs. translocation with deletion). Deletion of PTEN was seen in 16/95 tumors (16.8%) in CAU men while only 7/101 tumors (6.9%) in AA men (p<0.05). SPINK1 overexpression was present in 24/105 tumors (22.9%) from AA patients in contrast to 11/106 tumors (10.4%) from CAU patients (p<0.02). ERG gene fusion and SPINK1 overexpression were mutually exclusive in all cases. Furthermore, no deletion of PTEN was seen in the SPINK1 positive tumors.
Conclusions: Although clinical and pathologic factors in these AA and CAU cohorts were similar, molecular abnormalities between the two groups differed significantly. Our findings suggest possible pathobiologic differences between prostate cancers from AA and CAU men, with TMPRSS2-ERG gene fusion and PTEN deletion playing a lesser role and SPINK1 overexpression a larger role in AA as compared to CAU men. Further studies with clinical outcome data are needed in order to determine if these molecular differences explain, at least partially, the differences in incidence and mortality between these two racial groups.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 123, Monday Morning