Expression profiles of ERG, SPINK1, ETV1 and ETV4 in early onset prostate cancer: An immunohistochemical and RNA in-situ hybridization study on whole mount slides
Lu Z, Palanisamy N, Schultz D, Williamson SR, Carskadon S, Diaz-Insua M, Rogers CG, Stricker H, Peabody J, Wooju J, and Gupta N. Expression profiles of ERG, SPINK1, ETV1 and ETV4 in early onset prostate cancer: An immunohistochemical and RNA in-situ hybridization study on whole mount slides. Lab Invest 2018; 98:360.
Background: ETS family gene fusions are commonly seen in prostate cancer. ERG is more frequently overexpressed, followed by ETV1, ETV4, and ETV5. SPINK1 overexpression has been described in prostate cancer (PCa), but its prognostic value is controversial. All these alterations are generally mutually exclusive in PCa, but its expression profiles and the probable roles in young onset PCa have not been thoroughly explored. Design: A total of 153 Radical prostatectomy (RRP) specimens of patients younger than 55 year-old were retrieved from our institution. SPINK1 and ERG were detected by using immunohistochemical staining, ETV1 and ETV4 were detected by RNA in-situ hybridization. Expression of ERG, SPINK1, ETV1, and ETV4, and their association with various recorded clinicopathologic parameters were analyzed. Results: Age ranged from 33 to 55 years (Mean: 49). 70 (46%) Caucasians (CA), 61 (40%) African Americans (AA). Pre-operative PSA ranged from 0.6 to 52.7ng/ml (Mean: 7.15). 66(43%) patients had positive family history of PCa. Follow up period ranged from 1 to 123.7(Mean: 30.5) months. Biochemical Recurrence (BCR) was seen in 7/144 (5%). ERG expression was seen in majority of cases: 93/152 (61%) followed by SPINK1 in 73/152 (48%), ETV1 in 10/128(8%) and ETV4 in 3/48(6%). 37 cases (24%) showed both ERG and SPINK1 positivity. Table 1 lists association of these alterations with various clinicopathologic parameters. Out of 10 cases that were positive for ETV1, 6 cases showed additional marker positivity in whole mount sections: 2 cases (ERG+/SPINK1+) & 2 cases (ERG+/SPINK1-). 3/4 cases with isolated ETV1+ were nonorgan confined, remainder 7 cases were organ confined. ETV4 was positive in 3 cases (all AA patients), 2 cases showed additional marker positivity as follows: 1 case was SPINK1+ and 1 case was both ERG and SPINK1 positive. 2/3 cases were non-organ confined. Higher frequency of ERG expression was seen in younger aged patients (≤ 45 years old), CA patients and organ confined tumors 1. SPINK1 is often seen in AA patients and associated with non-organ confined disease 2. ERG and SPINK1 expression observed in 24% cases within different regions of a same tumor or different tumors within prostate gland. The clinical significance of this finding is uncertain as remains to be determined. 3. No association of any of the studied alteration was seen with BCR 4. Overall, tumors in young pts are low grade and stage and majority behave in an indolent fashion with low BCR rates.