EXPRESSION OF CD44 ISOFORMS IN RENAL-CELL TUMORS - POSITIVE CORRELATION TO TUMOR DIFFERENTIATION

CD44 isoforms have been implicated in tumor progression and embryogene sis. Primary renal cell tumors (n = 100) of various histopathological differentiation and grading stages were analyzed for expression of CD4 4 isoforms in comparison with noumalignant adult and fetal renal tissu es. Evaluations were performed by immuno-histochemistry using CD44 iso form-specific monoclonal antibodies and by reverse transcriptase polym erase chain reactions (RT-PCR). In the nonmalignant kidney no CD44 var iant isoforms wee detected. There was a significant increase in expres sion of CD44 standard (CD44s) and several variant isoforms (CD44v) in the course of tumor differentiation in clear cell carcinomas (n = 68) from stages G1 to G3 (P < 0.0001 for CD44s and isoforms containing CD4 4-6v, and P < 0.007 for those containing CD44-9v). Also, in chromophil ic cell carcinomas (n = 13), CD44 isoform expression correlated with g rading; ie, no CD44 expression was detected in G1 tumors, whereas in s imilar to 50% of the G2 tumors, CD44s, CD44-6v, and CD44-9v isoforms w ere present. Oncocytomas (n = 8), which are benign renal cell tumors, did not express CD44 isoforms, whereas invasive chromophobe cell carci nomas (n = 11) were positive for CD44s and CD44v isoforms. Transcript analyses by RT-PCR revealed that the upregulated isoforms in the carci noma cells contained exons 8 to 10 and 3, 8 to 10 in combination from the variant region. In conclusion, expression of variant CD44 isoforms was strongly correlated with grading and appears to mediate a more ag gressive phenotype to renal cell tumors.