Evidence for altered synthesis of human chorionic gonadotropin in gestational trophoblastic tumors

Tissue extracts of molar tissue or choriocarcinoma, blood, or urine of 21 women with gestational trophoblastic disease were analyzed for hCG and its subunits. The extracts or biologic fluids were initially chromatographed through a standardized Sephadex G-100 column. Each fraction was radioimmunoassayed in homologous hCG, hCGalpha, and hCGbeta assays. Extracts of four hydatidiform moles contained primarily hCG but no free alpha subunit of that hormone. One of the molar extracts contained a small amount of free hCGbeta not observed in the small amount of free hCGbeta not observed in the extracts of the other three moles. Plasma and urine samples from 18 women with localized or metastatic gestational trophoblastic disease contained hCG but no free alpha or beta subunits; the neoplasms of those patients readily responded to chemotherapy, and all patients have had no evidence of disease for at least one year. The major portion of immunologic hCG present in the biologic samples was indistinguishable from native hCG in its physical behavior on Sephadex G-100 chromatography. On the other hand, three women with widely metastatic tumors died in spite of extensive chemotherapy. Extracts of tumors from two of those patients contained hCG and free subunits of hCG. The urine and plasma of the third patient contained hCG and hCGalpha with the concentration of hCGalpha far exceeding that for hCG in urine. The results of these studies clearly show a disparity between the forms of hCG found in the normal placenta and pregnancy sera, as previously reported, and those found in the neoplastic trophoblast with varying degrees of anaplasia. The most striking finding was the absence of free circulating hCGalpha in the sera in patients with gestational trophoblastic disease which responded to chemotherapy, since free hCGalpha is readily detectable in the sera of normally pregnant women.