PRENEOPLASTIC AND NEOPLASTIC LESIONS OF RAT HEREDITARY RENAL-CELL TUMORS EXPRESS MARKERS OF PROXIMAL AND DISTAL NEPHRON

Long-Evans (Eker) rats carry a mutation that predisposes them to devel op spontaneous renal cell tumors of two morphologic patterns: solid ch romophilic masses or cystic lesions lined by eosinophilic cells. Previ ous studies have suggested that these tumors arise from the proximal t ubules. In the present study, lectin-binding characteristics and cytok eratin expression of various stages of hereditary rat renal epithelial neoplasia were examined to localize the portion of the nephron from w hich tumors arise. Lectin-binding histochemistry has been used as a ma rker of cell surface glycoprotein expression, thought to be important in the differentiation of benign from malignant epithelial lesions and in the determination of their cell of origin. The presence or absence of keratin intermediate filaments in the rat nephron has been used to identify nephron segments. The polyclonal antibody to high- and low-m olecular-weight cytokeratin stained the cells of the collecting ducts but not the proximal or distal tubules. Binding to the proximal tubule s by the lectins Conavalia ensiformis (Con A), Dolichas biflorus, Rici nus communis (RCA-1), and Triticum vulgare and to the distal tubules b y Con A, RCA-1, Arachis hypogaea (PNA) with and without neuraminidase, and the antibody for cytokeratins was demonstrated. The lectin bindin g and cytokeratin staining patterns of rat hereditary renal cell carci noma, adenoma and the preneoplastic lesions of atypical tubules and hy perplasias suggest that cystic adenomas arise from the distal nephron, principally the collecting duct, whereas the solid atypical tubules, hyperplasias, and adenomas arise from the proximal nephron, principall y the proximal tubule.