BACKGROUND: TMPRSS2:ERG fusion is the most common genetic event in prostate cancer (PCa). However, its association with prognosis is controversial. Overexpression of serine protease inhibitor Kazal-type 1 (SPINK1) was almost exclusively defined in ERG-negative PCa in most studies. This study aimed to determine the association between ERG and SPINK1 expression and the biological aggressiveness of PCa by analyzing their expression in incidental and metastatic cohorts. METHODS: A total of 143 cystoprostatectomy specimens of invasive bladder cancer and 98 biopsy specimens from de novo metastatic PCa were analyzed. The prostate gland of cystoprostatectomy specimens was fixed and sliced in step sections. Immunohistochemistry of ERG and SPINK1 was conducted, and the results were correlated with the clinicopathological characteristics of the patients. RESULTS: The overall prevalence of incidental cancer was 32.2% (46/143). The frequencies of both ERG and SPINK1 expression were not significantly different between incidental and metastatic cohorts (15.2% and 14.3%; P = 1.00, and 6.5% and 12.2%; P = 0.38, respectively). In the metastatic cohort, any pre-treatment factors were not significantly associated with the frequencies of ERG and SPINK1 expression. However, SPINK1 expression was significantly associated with a shorter time to castration-resistant PCa (CRPC) (P = 0.048). Meanwhile, overall survival was not significantly associated with the expression status of ERG and SPINK1 (P = 0.71). CONCLUSIONS: ERG and SPINK1 expression may not have significant influence on the metastatic behavior of PCa. SPINK1 expression was significantly associated with a shorter time to CRPC in metastatic PCa. The expression profile of ERG and SPINK1 may be a useful predictor for effect of androgen deprivation therapy in patients with metastatic castration-sensitive PCa.
BACKGROUND:TMPRSS2:ERG fusion is the most common genetic event in prostate cancer (PCa). However, its association with prognosis is controversial. Overexpression of serine protease inhibitor Kazal-type 1 (SPINK1) was almost exclusively defined in ERG-negative PCa in most studies. This study aimed to determine the association between ERG and SPINK1 expression and the biological aggressiveness of PCa by analyzing their expression in incidental and metastatic cohorts. METHODS: A total of 143 cystoprostatectomy specimens of invasive bladder cancer and 98 biopsy specimens from de novo metastatic PCa were analyzed. The prostate gland of cystoprostatectomy specimens was fixed and sliced in step sections. Immunohistochemistry of ERG and SPINK1 was conducted, and the results were correlated with the clinicopathological characteristics of the patients. RESULTS: The overall prevalence of incidental cancer was 32.2% (46/143). The frequencies of both ERG and SPINK1 expression were not significantly different between incidental and metastatic cohorts (15.2% and 14.3%; P = 1.00, and 6.5% and 12.2%; P = 0.38, respectively). In the metastatic cohort, any pre-treatment factors were not significantly associated with the frequencies of ERG and SPINK1 expression. However, SPINK1 expression was significantly associated with a shorter time to castration-resistant PCa (CRPC) (P = 0.048). Meanwhile, overall survival was not significantly associated with the expression status of ERG and SPINK1 (P = 0.71). CONCLUSIONS:ERG and SPINK1 expression may not have significant influence on the metastatic behavior of PCa. SPINK1 expression was significantly associated with a shorter time to CRPC in metastatic PCa. The expression profile of ERG and SPINK1 may be a useful predictor for effect of androgen deprivation therapy in patients with metastatic castration-sensitive PCa.
Authors: Camilo Arenas-Gallo; Jude Owiredu; Ilon Weinstein; Patrick Lewicki; Spyridon P Basourakos; Randy Vince; Bashir Al Hussein Al Awamlh; Fredrick R Schumacher; Daniel E Spratt; Christopher E Barbieri; Jonathan E Shoag Journal: Nat Rev Urol Date: 2022-08-09 Impact factor: 16.430