PT  - JOURNAL ARTICLE
AU  - Leinonen, Katri A.
AU  - Tolonen, Teemu T.
AU  - Bracken, Hazel
AU  - Stenman, Ulf-Håkan
AU  - Tammela, Teuvo L.J.
AU  - Saramäki, Outi R.
AU  - Visakorpi, Tapio
TI  - Association of SPINK1 Expression and <em>TMPRSS2:ERG</em> Fusion with Prognosis in Endocrine-Treated Prostate Cancer
AID  - 10.1158/1078-0432.CCR-09-2505
DP  - 2010 May 15
TA  - Clinical Cancer Research
PG  - 2845--2851
VI  - 16
IP  - 10
4099  - http://clincancerres.aacrjournals.org/content/16/10/2845.short
4100  - http://clincancerres.aacrjournals.org/content/16/10/2845.full
SO  - Clin Cancer Res2010 May 15; 16
AB  - Purpose: The aim of the study was to examine whether TMPRSS2:ERG fusion or SPINK1 protein expression is associated with hormone responsiveness of prostate cancer and can thus be used as a biomarker.Experimental Design: Diagnostic needle biopsies from prostate cancer patients primarily treated by endocrine therapy were evaluated for TMPRSS2:ERG fusion with fluorescence in situ hybridization and SPINK1 protein expression with immunohistochemistry.Results: The frequency of TMPRSS2:ERG fusion in 178 biopsies of hormonally treated patients was 34%. Of the fusion-positive cases, 71% showed deletion between the two genes, and 23% showed gain of the fusion. The fusion was associated with high Ki-67 staining (P = 0.001), age at diagnosis (P = 0.024), and tumor area (P = 0.006), but not with Gleason score, T stage, M stage, prostate-specific antigen (PSA), or progression-free survival. Strong positive SPINK1 expression was found in 11% (21 of 186) of the biopsies. SPINK1-positive cases had significantly shorter progression-free survival compared with SPINK1-negative cases (P = 0.001). The expression was not associated with any other clinicopathologic variables studied. In a multivariate analysis, SPINK1 expression showed independent prognostic value, with a relative risk of 2.3 (95% confidence interval, 1.1-4.6). SPINK1 expression and the fusion were not associated with each other.Conclusions: There was no association between TMPRSS2:ERG fusion and prognosis, suggesting that TMPRSS2:ERG rearrangement does not implicate hormone dependence of the cancer. SPINK1 expression, found in ∼10% of prostate cancers, was associated with aggressive form of the disease and could serve as a biomarker in endocrine-treated prostate cancer. Clin Cancer Res; 16(10); 2845–51. ©2010 AACR.