Altered messenger RNA and protein expressions for insulin-like growth factor family members in clear cell and papillary renal cell carcinomas

Background: The purpose of the present paper was to describe the pattern of expression of insulin-like growth factor (IGF-I) and its regulatory binding proteins (IGFBP) in renal cell carcinoma (RCC). Methods: The expressions of mRNA and protein for various IGF members were assessed in 24 paired normal and malignant human renal tissues (16 clear cell and 8 papillary RCC) using semiquantitative reverse transcription-polymerase chain reaction and immunohistochemistry. Paired tissue samples were also obtained from six patients with oncocytoma in order to compare the specificity of changes in IGF/IGFBP expression between tumors derived from proximal (RCC) and distal (oncocytoma) tubular epithelium. Results: Clear cell RCC were characterized by significant increases in the mRNA expression of IGF-I, IGFBP-3 and IGFBP-6 while papillary RCC exhibited down-regulated expression of IGF-I, IGFBP-4 and IGFBP-5. The IGFBP-2, IGFBP-4 and IGFBP-5 mRNA were down-regulated in oncocytomas. Semiquantitative assessment of immunohistochemical staining demonstrated significant increases in epithelial associated IGF-I and IGFBP-3 in clear cell RCC, increased IGFBP-5 protein in papillary RCC and no significant changes in IGF/IGFBP protein expression in oncocytoma. Conclusions: The expression of IGF-I and certain IGFBP is significantly altered in RCC compared with normal renal tissue and oncocytomas. This altered expression is differentially regulated according to the histologic subtype of RCC, and suggests that the IGF/IGFBP axis may play an important role in determining the malignant phenotype of RCC.