Association of SPINK1 Expression and TMPRSS2:ERG Fusion with Prognosis in Endocrine-Treated Prostate Cancer

被引:84
|
作者
Leinonen, Katri A. [1 ]
Tolonen, Teemu T. [1 ,3 ]
Bracken, Hazel [1 ]
Stenman, Ulf-Hakan [4 ]
Tammela, Teuvo L. J. [2 ]
Saramaki, Outi R. [1 ]
Visakorpi, Tapio [1 ]
机构
[1] Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33014 Tampere, Finland
[2] Tampere Univ Hosp, Dept Urol, Tampere, Finland
[3] Vaasa Cent Hosp, Dept Pathol, Vaasa, Finland
[4] Univ Helsinki, Dept Clin Chem, Cent Hosp, SF-00100 Helsinki, Finland
基金
芬兰科学院;
关键词
TRYPSIN-INHIBITOR; GENE FUSIONS; ABERRATIONS; RECEPTOR; TATI;
D O I
10.1158/1078-0432.CCR-09-2505
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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, Mstage, 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 similar to 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. (C) 2010 AACR.
引用
收藏
页码:2845 / 2851
页数:7
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