PRODUCTION OF TROPHOBLASTIC HORMONES BY TRANSITIONAL-CELL CARCINOMA OF THE BLADDER - ASSOCIATION TO TUMOR STAGE AND GRADE

Cancer registration statistics of economically advanced countries indi cate that bladder carcinoma incidence ranks: fourth in men and eighth in women, but a reliable tumor marker for predicting the disease cours e is still lacking. We designed an immunohistochemical study to compre hensively assess the trophoblastic hormone production profile of trans itional cell carcinoma (TCC) of the bladder. Moreover, we correlated h istological differentiation and tumor stages with marker expression an d, finally, evaluated a potential tumor origin of hCG beta core-fragme nt (hCG beta cf). To this end, formalin-fixed, paraffin-embedded tumor tissues from 104 patients with urothelial neoplasms of various histol ogical grades (23 GI, 24 GII, and 38 GIII) and staple (19pTis, 21pTa, 29pT1, and 35pT2-T4) were analyzed by the immunoperoxidase technique u sing our own well-characterized monoclonal antibodies against the glyc oprotein hormones human chorionic gonadotropin (hCG) and its derivativ es hCG alpha, hCG beta, hCG beta cf, luteinizing hormone (LH, LH beta) , follicle-stimulating hormone (FSH, FSH beta), and the protein hormon es placental lactogen (hPL) and growth hormone (hGH-V/N). Overall, tro phoblastic hormone immunoreactivity was found in 36% of TCC. Detailed analysis showed 35% hCG beta, 17% hCG beta cf, 9% hCG alpha, 4% hCG, a nd 2% hPL-positive cases. The tumors produced neither GH-N, placental GH-V, nor the pituitary gonadotropins FSH/FSH beta and LH/LH beta. Mar ker positivity significantly increased with high-grade lesions (26% GI -v 55% GIII-TCC) and advanced tumor stages (24% pTa v 63% greater than or equal to pT2). Hormone immunoreactivity was frequently observed in highly proliferating areas. Our finding, together with recent structu ral and clinical studies, strongly suggest that these hormones, or der ivates thereof, might act as local tumor growth factors. Normal urothe lium, urothelial papillomas, and carcinoma in situ showed no positive reactions. All tumors producing hCG-derived molecules were negative fo r the concommitantly analyzed neuroendocrine markers chromogranin A, s ynaptophysin, and neuron-specific enolase (NSE). In summary, one third of TCC ectopically produce trophoblastic hormones, which is specifica lly correlated with stage and grade. Apart from hCG beta (97% of the m arker-positive cases), the intracellular occurrence of hCG beta cf, ap parently the second most frequently produced marker, was surprising, a nd there was also a lesser degree free hCG alpha and intact hole-hormo ne expression. The placental protein hormones PL and GH-V are not appr opriate tumor marker candidates. Finally, our histogenetic findings su pport a metaplastic origin of the hCG producing choriocarcinomatous ph enotype of some TCC. Copyright (C) 1998 by W.B. Saunders Company.