Objective: Human chorionic gonadotropin (hCG) is a marker of trophoblastic tumors, and the serum concentration of the free β-subunit (hCGβ) is an independent prognostic marker in several nontrophoblastic cancers. hCGβ is encoded by six genes, of which the type II genes (hCGβ 3/9, 5 and 8) are thought to be upregulated in relation to type I genes (hCGβ 6/7) in cancer. Method: We developed a novel quantitative RT-PCR method for the quantification of the relative expression levels of the two groups of hCGβ genes and analyzed 28 bladder tumors and 15 urine samples. Results: We found a higher relative expression level of type II genes in malignant compared with benign urothelia (p = 0.016) and in exfoliated urinary cells from cancer patients compared with those from benign controls (p = 0.026). The expression level was increasing with higher stage (p = 0.014) and grade (p = 0.001) and tended to be higher in relapsing tumors (p = 0.059). Conclusion: The increased hCGβ concentrations in body fluids of patients with aggressive bladder cancer may be due to overexpression of type II genes. Quantification of the relative mRNA expression levels of the hCGβ type I and II genes in urine cells should be further studied as a potential noninvasive tool for the diagnosis and follow-up of bladder cancer.

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