Clonal evaluation of early onset prostate cancer by expression profiling of ERG, SPINK1,ETV1, andETV4on whole mount radical prostatectomy tissue

ABSTRACT Expression profiles of ETS related genes and SPINK1 in early onset prostate cancer have not been thoroughly explored. We retrieved 151 radical prostatectomy specimens from young men with prostate cancer (<55yrs) and characterized the expression of ERG, SPINK1, ETV1 and ETV4 by dual immunohistochemistry and dual RNA in-situ hybridization. Age, race, family history, preoperative prostate-specific antigen, biochemical recurrence and pathological variables using whole mount radical prostatectomy tissue were collected. 313 tumor nodules from 151 men including 68 (45%) Caucasians and 61 (40%) African Americans. Positive family history of prostate cancer was observed in 65 (43%) patients. Preoperative prostate-specific antigen ranged from 0.3 to 52.7 ng/ml (mean 7.04). Follow-up period ranged from 1 to 123.7 months (Mean 30.3). Biochemical recurrence was encountered in 8/151 (5%). ERG overexpression was observed in 85/151 (56%) cases, followed by SPINK1 in 61/151 (40%), ETV1 in 9/149 (6%), and ETV4 in 4/141 (3%). There were 25/151 (17%) cases showing both ERG and SPINK1 overexpression within different regions of either the same tumor focus or different foci. Higher frequency of ERG overexpression was seen in younger patients (≤ 45 years old) (76% vs. 49%, p = 0.002213), Caucasian men (71% vs. 41% p = 0.000707), organ-confined tumors (64% vs. 33%, p = 0.00079), and tumors of Grade Groups 1 and 2 (62% vs. 26%, p = 0.008794). SPINK1 overexpression was more in African American men (68% vs. 26%, p = 0.00008), in tumors with high tumor volume (> 20%) and with anterior located tumors. ETV1 and ETV4 demonstrated rare overexpression in these tumors, particularly in the higher-grade tumors. This study expands the knowledge of the clonal evolution of multifocal cancer in young patients and support differences in relation to racial background and genetics of prostate cancer.