Immunoreactivity for inhibin in renal cell tumors correlates with differentiation

Raghava Munivenkatapa, M.D., Cinthia B. Drachenberg, M.D., Steven G. Silverberg, M.D., John C. Papadimitriou, M.D.,Ph.D.

Department of Pathology, University of Maryland School of Medicine

Members of the TGF-8 superfamily of intercellular signaling factors include TGF-8s, activins and inhibins. Their participation in the control of the cell cycle and apoptosis has been postulated. The role of TGF-8 has been extensively studied in renal diseases and particularly in the progression of glomerulonephritis to sclerosis. TGF-8 affects proliferation and differentiation in a variety of cell types, induces the synthesis of extracellular matrix proteins, regulates matrix proteases and antiproteases and modulates integrin expression. The role of these molecules in the formation of mesoderm of which the kidney is also formed, has also been implicated. In tumor pathology the demonstration of inhibin has been considered as diagnostic of ovarian or adrenal cortical origin. Based on the above data, however, indicating a potential role of inhibin in the kidney, we studied the presence of inhibin in renal neoplasms. We examined by immunohistochemistry 16 renal tumors (5 clear cell renal cell carcinomas (RCC), 5 papillary RCC, 3 RCC with oncocytic features, 2 sarcomatoid RCC and 1 oncocytoma). Results: Most of the cases showed some degree of positivity, being highest i.e. +++ (3/3) in RCC with oncocytic features and oncocytoma and ++/+++ (4/5) in papillary RCC. The weakest positivity (+/-) 5/5 was noted in the clear cell RCC cases, whereas the 2 sarcomatoid RCC were completely negative. The benign kidney tissue showed intense positivity in the tubules in all cases. The glomeruli were consistently negative. Conclusions: Inhibin is shown to be a marker for both normal as well as neoplastic renal tubular tissue. Interestingly the benign tumors or the RCC with features of less aggressive behavior were most intensely positive for inhibin. These data could be interpreted by postulating a role of inhibin in the differentiation of tumor cells as well as control of proliferation and antiapoptotic processes by regulation of p57kip2 in cell cycle.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Diagnostic Markers.