SPINK1 protein expression and prostate cancer progression

Abstract

Purpose: SPINK1 overexpression has been described in prostate cancer and is linked with poor prognosis in many cancers. The objective of this study was to characterize the association between SPINK1 overexpression and prostate cancer-specific survival.

Experimental design: The study included 879 participants in the U.S. Physicians' Health Study and Health Professionals Follow-Up Study, diagnosed with prostate cancer (1983-2004) and treated by radical prostatectomy. Protein tumor expression of SPINK1 was evaluated by immunohistochemistry on tumor tissue microarrays.

Results: Seventy-four of 879 (8%) prostate cancer tumors were SPINK1 positive. Immunohistochemical data were available for PTEN, p-Akt, pS6, stathmin, androgen receptor (AR), and ERG (as a measure of the TMPRSS2:ERG translocation). Compared with SPINK1-negative tumors, SPINK1-positive tumors showed higher PTEN and stathmin expression, and lower expression of AR (P < 0.01). SPINK1 overexpression was seen in 47 of 427 (11%) ERG-negative samples and in 19 of 427 (4%) ERG-positive cases (P = 0.0003). We found no significant associations between SPINK1 status and Gleason grade or tumor stage. There was no association between SPINK1 expression and biochemical recurrence (P = 0.56). Moreover, there was no association between SPINK1 expression and prostate cancer mortality (there were 75 lethal cases of prostate cancer during a mean of 13.5 years follow-up; HR = 0.71; 95% confidence interval, 0.29-1.76).

Conclusions: Our results suggest that SPINK1 protein expression may not be a predictor of recurrence or lethal prostate cancer amongst men treated by radical prostatectomy. SPINK1 and ERG protein expression do not seem to be entirely mutually exclusive, as some previous studies have suggested.

Figure 1

Immunohistochemistry for nuclear marker ERG (left hand panel) and cytoplasmic marker SPINK1 (right hand panel) showing diffuse positive staining in the exact same tumor cores from a case of prostate adenocarcinoma Gleason score 4+4 (A–B; x20) and from a case of prostate adenocarcinoma Gleason score 3+3 (C–D; x20).

Figure 2

Dual immunohistochemical staining for nuclear marker ERG (red) and cytoplasmic marker SPINK1 (brown) showing positive staining in discrete foci of whole tumor sections from two separate cases (A–C; B–D) of prostate adenocarcinoma (x4 (left hand column); x40(right hand column)). Note in panel B there areas of dual positivity for SPINK1 and ERG (top) and areas of tumor negative for both markers (bottom).