Parathyroid hormone-related protein is an independent prognostic factor for renal cell carcinoma

Abstract

BACKGROUND. Parathyroid hormone-related protein (PTHrP) has been shown to be the principal cause of humoral hypercalcemia associated with renal cell carcinoma (RCC). Recent studies have demonstrated that the amino-terminal region of PTHrP has growth factor-like activities, suggesting it may play a role in the development of RCC. In this study, expression of the carboxy- terminal region of PTHrP was assessed immunohistochemically and its significance in predicting the prognosis of RCC was studied. METHODS. Forty radical nephrectomy specimens were immunostained with a murine monoclonal antibody (9H7) against the carboxy-terminal region (amino acids 109-141) of PTHrP using the streptavidin-peroxidase enzyme conjugate method. Staining intensity was evaluated semiquantitatively and compared with clinicopathologic features of the corresponding RCC. RESULTS. Immunoreactivity to 9H7 was observed to be localized to the cytosol of tumor cells at various staining intensities. There were 30 cases (75.0%) with strong staining and 10 cases (25.0%) in which staining was weak or nonexistent. Staining intensity showed no significant correlation with gender, tumor greatest dimension, stage, or grade. Tumors of the clear cell type expressed PTHrP to a significantly greater extent than tumors of the granular cell type. Tumor recurrence was significantly greater in the weakly stained or unstained group compared with the strongly stained group (P = 0.035). Multivariate analysis indicated that PTHrP expression and tumor stage were equally significant prognostic indicators in RCCs measuring <10 cm in greatest dimension. CONCLUSIONS. Evident PTHrP(109-141) expression is present in the majority of RCCs. The results of the current study indicate PTHrP(109- 141) may be a possible marker of cellular differentiation and may be useful for predicting recurrence free survival in RCC patients after radical nephrectomy.