Abstract
BackgroundThe expression status of apoptotic regulators, such as caspases and inhibitors of apoptosis proteins (IAPs), could reflect the aggressiveness of tumors and, therefore, could be useful as prognostic markers. We explored the associations between tumor expression of caspases and IAPs and clinicopathological features of prostate cancer – clinical and pathological T stage, Gleason score, preoperative serum PSA levels, perineural invasion, lymph node involvement, surgical margin status and overall survival – and evaluated its capability to predict biochemical progression after radical prostatectomy.MethodsProtein expression of caspases (procaspase-8, cleaved caspase-8, procaspase-3, cleaved caspase-3, caspase-7 and procaspase-9) and IAPs (cIAP1/2, cIAP2, NAIP, Survivin and XIAP) was analyzed by immunohistochemistry in radical prostatectomy samples from 84 prostate cancer patients. Spearman’s test, Kaplan-Meier curves, and univariate and multivariate Cox proportional hazard regression analysis were performed.ResultscIAP1/2, cIAP2, Survivin, procaspase-8, cleaved caspase-8, procaspase-3 and caspase-7 expression correlated with at least one clinicopathological feature of the disease. Patients negative for XIAP, procaspase-3 or cleaved caspase-3 had a significantly worse prognosis. Of note, XIAP, procaspase-3 and cleaved caspase-3 were predictors of biochemical progression independent of Gleason score and pathological T stage.ConclusionsOur results indicate that alterations in the expression of IAPs and caspases contribute to the malignant behavior of prostate tumors and suggest that tumor expression of XIAP, procaspase-3 and cleaved caspase-3 may help to identify prostate cancer patients at risk of progression.
Highlights
The expression status of apoptotic regulators, such as caspases and inhibitors of apoptosis proteins (IAPs), could reflect the aggressiveness of tumors and, could be useful as prognostic markers
Expression of XIAP, procaspase-3 and cleaved caspase-3 inversely correlated with the occurrence of biochemical progression, indicating that these proteins can have a role as prognostic markers (Tables 3 and 4)
We found positive correlations between expression of some caspases and adverse clinicopathological features: procaspase-8 correlated with both clinical and pathological T stages, cleaved caspase-8 correlated with preoperative serum PSA, and caspase-7 correlated with Gleason score and the presence of lymph node metastasis
Summary
The expression status of apoptotic regulators, such as caspases and inhibitors of apoptosis proteins (IAPs), could reflect the aggressiveness of tumors and, could be useful as prognostic markers. We explored the associations between tumor expression of caspases and IAPs and clinicopathological features of prostate cancer – clinical and pathological T stage, Gleason score, preoperative serum PSA levels, perineural invasion, lymph node involvement, surgical margin status and overall survival – and evaluated its capability to predict biochemical progression after radical prostatectomy. There are two major apoptotic pathways: the extrinsic and the intrinsic (or mitochondrial) apoptotic pathways These apoptotic pathways converge in the activation of executioner caspases, which proteolyze a plethora of substrates leading to the death of the cell [3]
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