Clinical significance and EZH2, ERG and SPINK1 protein expression in pure and mixed ductal adenocarcinoma of the prostate

Background: Although ERG and SPINK1 molecular alterations have been studied in acinar and ductal adenocarcinoma of the prostate, EZH2 expression has not been previously evaluated in ductal adenocarcinoma. Methods: We collected cases of pure and mixed ductal adenocarcinoma of the prostate and evaluated clinical significance and EZH2, ERG, and SPINK1 protein expression. Results: We investigated 61 ductal adenocarcinomas, 22 pure and 39 mixed ductal/acinar. Except for tumor growth pattern, none of the clinical parameters studied significantly differed between pure and mixed tumors. Thirty-five percent of ductal adenocarcinomas were organ confined, 15% displayed seminal vesicle invasion. Lymph node and distal metastasis occurred in 13% and 24% of cases, respectively; 34% of patients experienced biochemical failure, 7% died of disease. Ninety-eight percent of tumors expressed EZH2; in 80% of cases >50% of tumor cells were positive. ERG and SPINK1 were expressed in 20% and 36% of cases, respectively. There was no difference in protein expression between pure and mixed ductal adenocarcinomas. ERG expression tended to be lower, and SPINK1 higher than reported for acinar tumors. Biochemical failure, metastasis and death did not differ between EZH2, ERG, and SPINK1 positive and negative patients, nor between 50% expression of SPINK1 and EZH2, respectively. Conclusions: Pure and mixed ductal adenocarcinomas have similar clinical behavior and molecular alterations. Higher EZH2 and SPINK1 protein expression, compared to acinar prostatic adenocarcinoma, might account for the more aggressive clinical course of ductal adenocarcinoma. Histol Histopathol 34, 381-390 (2019)