Prognostic significance of osteopontin expression in human prostate cancer

Abstract

To test the hypothesis that expression of osteopontin (OPN), an integrin-binding glycoprotein, can independently predict the potential aggressiveness of prostate cancer, the status of OPN expression in benign and malignant prostate cancer cell lines and tissues was analysed by Western blot and immunohistochemistry. Amongst the four prostate cell lines analysed, the level of OPN expressed in the benign PNT-2 cells was set at 1, the relative level of OPN expressed in the weakly malignant cell line LNCaP was increased to 1.5. In the highly malignant cell lines Du-145 and PC-3, the level of OPN expression was further increased to 2.9 and 4.4, respectively. An increased expression of OPN was also observed in the prostate tissue samples. When the level of OPN in normal tissue was set at 1, its level in benign prostate hyperplasia (BPH) was similar at 0.99 6 0.2, whereas the OPN level in the highly malignant carcinoma tissue was greatly increased by nearly 6-fold to 5.9 6 0.3. Amongst the 116 cases examined immunocytochemically, of the 10 normal cases, 3 (30%) were unstained and 7 (70%) stained weakly positive (1). Amongst the 36 BPH samples, 32 (89%) stained weakly positive (1) and 4 (11%) were unstained (2). For the 70 carcinomas analysed, 31 (44%) stained strongly positive (111), 20 (29%) stained moderately positive (11) and 19 (27%) stained weakly positive (1). These results showed that the level of OPN expressed between the normal and the BPH samples was not significantly different (Fisher's exact test, p 5 0.16). However, in comparison to that in the BPH samples, the expression of OPN in the carcinoma tissues was significantly increased (Chi-square test, p < 0.0001). Kaplan-Meier survival analysis showed that the increased level of OPN expression was significantly (n 5 70, p 5 0.03) associated with reduced survival time of the patients. The OPN expression was increased with the increasing Gleason scores of the carcinomas (Chi-square test, p < 0.001). The results in our study support our hypothesis and suggest that the increased OPN level may be involved in the malignant transformation of prostate epithelial cells and OPN expression level is an important determinant for patient survival. ' 2005 Wiley-Liss, Inc.Key words: prostate carcinoma; osteopontin; benign prostate hyperplasia (BPH); Gleason scores; patient survival Prostate cancer has become the most common male cancer and the second leading cause of death from male malignant disease in the United States and Europe, and this disease kills more than 40,000 men per year in the developed world. 1,2 Despite the increasing incidence, the molecular basis of prostate cancer progression, invasion and metastasis is still not fully understood. The complicated molecular pathology of prostate cancer may involve a series of sequential genetic events, which cause the initiation and progression of the malignant changes of prostate epithelial cells. The complicated genetic events responsible for tumorigenicity and metastasis of prostate cancer may be classified in a simple ...

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