Selective expression of trophoblastic hormones by lung carcinoma: Neurendocrine tumors exclusively produce human chorionic gonadotropin alpha-subunit(hCG alpha)

Recent findings suggest that glycoprotein- and protein hormones act as loca l auto/paracrine growth/differentiation factors in normal and malignant tis sue. An imbalanced or even selective production of human chorionic gonadotr opin-alpha (hCG alpha) by neuroendocrine tumors in various organs has been reported. In this context, the ectopic production of trophoblastic hormones by lung c arcinoma has not been investigated systemically. Because the determination of serum levels of hCG alpha are flawed by a number of factors, we designed an immunohistochemical study to precisely assess the comprehensive paraneo plastic auto-/paracrine hormone production by lung carcinoma of various his tological types. To this end, 90 patients with primary lung neoplasms (40 neuroendocrine tum ors, 29 adenocarcinomas, 20 squamous cell carcinomas, and 1 adenosquamous c arcinoma) were analyzed by our well characterized monoclonal antibodies (ma bs) against the glycoprotein hormones hCG, and its derivatives hCG alpha, h CG beta, hCG beta core-fragment (hCG beta cf), luteinizing hormone (LH, LH beta), follice-stimulating hormone (FSH, FSH beta), and the protein hormone s placental lactogen (PL) and growth hormone (GH). Overall, trophoblastic hormone immunoreactivity was Found in 31% (28/90) of all lung carcinomas, regardless of histological differentiation. Detailed analysis showed 23% (21/90) hCG alpha-, 7% (6/90) hCG beta-, and 2% (2/90) hCG beta cf-positive cases. The tumors produced neither the intact heterodi mer hCG, nor the other placental protein hormones PLA/B and GH-V, or the hC G-related pituitary gonadotropins FSH/FSH beta and LH/LH beta. With regard to histological differentiation, it appeared that neuroendocrine tumors exc lusively pro-histological tumor grade. Thirty-eight percent (15/40) of all neuroendocrine neoplasms were hCG alpha-positive, and marker positivity inc reased with more mature, highly differentiated tumors (20% of Mall cell neu roendocrine carcinomas versus 90% of atypical and typical carcinoids). This is in striking contrast not only to trophoblastic malignancies and testicu lar germ cell tumors, but also to nontrophoblastic tumors, such as gynecolo gical and urothelial malignancies, 60% of which produce hCG beta and where marker positivity correlates with poor histological tumor differentiation. In conclusion, free hCG alpha, but not hCG beta, is a useful marker for neu roendocrine differentiation in primary lung tumors. The fact that it is pre ferentially produced by the differentiated tumor types (carcinoids) points to a putative biological function in these tissues. The few hCG beta-positi ve NSCLC must not be confounded with primary mediastinal choriocarcinoma. C opyright (C) 2000 by W.B. Saunders Company.