KPNA2/ERG Coexpression is Associated with Early Recurrence in Advanced Prostate Cancers

Most prostate cancers (PC) overexpress the ERG oncogene and karyopherin α 2 (KPNA2). These genes play a role in prostatic carcinogenesis, but their prognostic significance is still debated. The aim of this study was to determine the prognostic significance of ERG and KPNA2 expression, and their association to early prostate-specific antigen (PSA) biochemical recurrence in advanced PC with lymph node metastases. A series of 65 consecutive pN1 M0 R0 PC samples obtained by radical prostatectomy with lymphadenectomy has been analyzed for ERG and KPNA2 expression by immunohistochemistry. For each case, the following clinical data were collected: age, preoperative serum PSA levels, Gleason grade group, TNM stage, and follow-up. PC recurrence was investigated by serum PSA assay and defined by a PSA concentration >0.2 ng/mL after a nadir of <0.1 ng/mL following radical prostatectomy. ERG-positive staining was found in 25/65 cases (38%), and KPNA2 in 56/65 cases (86%); neither was detected in normal prostatic tissue. Immunohistochemical concordance was found between primary tumor and lymph node metastases in 24/25 (96%) of ERG and 53/56 (95%) of KPNA2-positive cases. The follow-up was known in all cases, and early PSA recurrence occurred in 25/65 cases (38%). ERG positivity, both alone and in conjunction with KPNA2 positivity, was strongly associated with early PSA recurrence [both ERG+ and KPNA+, odds ratio: 22.2 (95% confidence interval, 6.0-82.3); ERG+ alone odds ratio: 17.9 (95% confidence interval, 5.1-63.5); P<0.0001 for both]. KPNA2 expression was significantly associated with the tumor stage (P<0.00001). The results suggest that the ERG+ phenotype might be selected in metastasis-initiating clones. ERG and KPNA2 may have a prognostic value, and their positivity in PC might warrant more aggressive treatments.