Expression of human chorionic gonadotropin beta-subunit type I genes predicts adverse outcome in renal cell carcinoma

Expression of the free beta-subunit of human chorionic gonadotropin (hCGbeta) in malignant tumors is frequently associated with aggressive disease. The pretreatment serum concentration of hCGbeta is an independent prognostic variable in renal cell carcinoma (RCC). The three so-called type II genes (hCGbeta 3/9, 5, and 8) have been shown to be up-regulated in relation to type I genes (hCGbeta 6/7) in some malignant tumors. We developed a reverse transcription-polymerase chain reaction method for quantification of relative levels of the mRNAs for the two types of hCGbeta genes and studied the association between the expression in RCC tissue (n = 104) and clinical outcome. hCGbeta mRNA expression was detected in 40% (42 of 104) of the tumors, and in 40 of these (93%), this consisted of hCGbeta type I mRNA only, whereas type II hCGbeta mRNA was detected in two samples. hCGbeta mRNA expression was significantly associated with a shorter disease-specific (log-rank P = 0.023; median survival 1.4 versus 7.9 years) and overall survival (log-rank P = 0.011). In a Cox regression model, stage (P < 0.0001) and hCGbeta mRNA expression (P < 0.0001) were independent prognostic variables. We conclude that expression of type I hCGbeta genes indicates adverse prognosis in RCC.