The majority of the newly diagnosed CaP patients have clinically organ-confined disease [22
]. Although, nomograms based on pre- and post-operative parameters offer some information about patients’ prognosis, limited knowledge about which CaP is likely to progress, as well as, when it will recur severely impedes individualized selection of therapy and subsequent prediction of outcome [23
]. Recent studies have shown that chemokines, cytokines and other proteins that are associated with inflammatory processes may function in promoting tumor invasion and metastasis [24
]. Furthermore, some of these molecules, such as cyclooxygease-2 have shown prognostic potential for predicting CaP progression [18
]. In this study, with a minimum 6 year on all patients, we demonstrate that the expression of OPN, in radical prostatectomy specimens is independently associated with biochemical recurrence. Furthermore, OPN and LI-8 may be early predictors of disease progression.
In prostate tissues, OPN levels have been shown to be elevated in carcinoma when compared to normal and benign prostatic hyperplasia tissues [9
]. Consistent with these findings, we found that benign prostate specimens stained for OPN with low intensity. Furthermore, we observed that OPN staining correlated with Gleason sum (P < 0.001; logistic regression analysis; unpublished results. This may explain why when OPN staining is included in the multivariate model, Gleason sum did not reach statistical significance in predicting biochemical recurrence even when included as a categorized (< 8, ≥ 8). Although the over expression of OPN has been previously shown to correlate with poor survival, our study is the first to report that high OPN staining may indicate biochemical recurrence in the future. OPN was found to be independently associated with biochemical recurrence within 72 months. The high sensitivity and specificity (~ 76%) of OPN staining to predict biochemical recurrence also suggest that it may be a clinically useful marker for predicting biochemical recurrence. The observation that high intensity staining of normal glands surrounding tumor cells for both IL-8 and OPN proteins is an indication of the possible role of the paracrine induction of pro-inflammatory factors in the development of reactive stroma, which in turn, promotes tumor progression [27
The expression of IL-8 mRNA has been shown to correlate with Gleason sum and pathologic stage [13
], but whether it independently associates with biochemical recurrence has not been evaluated. In our study, IL-8 expression correlated with Gleason sum (P = 0.019; logistic regression analysis) but not with clinical stage (p = 0.8; unpublished results). Furthermore, IL-8 staining also does not independently associate with biochemical recurrence within 72 months.
It is noteworthy that among the group of CaP patients who recurred, OPN was able to distinguish between those who recurred before 24 months and those recurring after 24 months in the multivariate model. Although, IL-8 staining score when included by itself in the multivariate model was not an early predictor of biochemical recurrence, when included in the model along with the OPN staining, it did contribute to recognizing those patients who will have early biochemical recurrence, and hence may be at risk for systemic disease. This result is consistent with the role of OPN and IL-8 in cancer metastasis and progression.
Taken together our study shows that OPN in radical prostatectomy specimens is independently associated with CaP progression i.e., biochemical recurrence, and when combined with margin status, can stratify patients into different risk categories for developing biochemical recurrence within six years. In addition, OPN either alone or together with IL-8 and SVI may be able to stratify patients at risk for early disease progression.