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Background: There have been 12 documented cases of choriocarcinoma arising in the urinary bladder, either alone or in combination with other epithelial tumors. It has been shown that some high-grade transitional cell carcinomas (TCC), without obvious syncytiotrophoblastic elements, can produce human chorionic gonadotrophins (HCG)., Methods: A case of choriocarcinoma, in association with high-grade TCC of the renal pelvis, was encountered in an 80-year-old man. For additional evaluation of HCG production by TCC, 25 consecutive cases of invasive high-grade TCC of the bladder were stained with an anti-HCG antibody. Immunogold staining also was performed in two of the cases studied., Results: Immunoperoxidase staining of the renal pelvis tumor showed focal positivity for HCG within the TCC and a more intense reaction as the tumor cells differentiated into choriocarcinoma elements. Seven of the 25 cases (28%) displayed varying degrees of reactivity within individual cells or groups of cells. In an additional case, typical syncytiotrophoblastic giant cells without cytotrophoblasts were seen in a high-grade TCC. Immunogold studies demonstrated positive labeling in the cytoplasm of carcinoma cells in a case of TCC without syncytiotrophoblasts and in the syncytiotrophoblastic giant cells in the one case in which these were present., Conclusions: The findings support a metaplastic origin of cases of choriocarcinoma arising primarily in the urothelial tract.

Treatment of human choriocarcinoma cells with cytochalasin B at the doses of inhibiting cell division but not inhibiting nuclear division led to in vitro formation of the multinucleated syncytiotrophoblast-like ( STL ) cells. A concomitant increase in human chorionic gonadotropin (hCG) secretion per cell was noted. Immunocytochemical staining demonstrated the predominant localization of hCG in the STL cells. These results indicate that multinucleation stimulates hCG synthesis and secretion in the choriocarcinoma cells.

The secretory potential of human chorionic gonadotropin (hCG) in eight strains of human choriocarcinoma cell lines was examined in vitro and the correlation between the secretory potential and certain cell biological characteristics was studied. Multinucleated giant cells (syncytiotrophoblast-like cells) were occasionally observed only in high hCG-secreting cell lines in accordance with inhibition of growth. Appearance of abundant dilated rough endoplasmic reticulum and aggregated glycogen particles in the cytoplasm seemed to represent ultrastructural characteristics of high hCG-secreting cell lines. A shift of nuclear DNA to hyperploidy, its wide distribution, and S phase accumulation of cells by flow cytometry were also characteristic of them. However, no correlation was noted between the hCG secretory potential and population doubling time of the cell lines in vitro.

Human chorionic gonadotrophin(hCG)-producing cells in the human placenta and in testicular germ cell tumors have been investigated by ultrastructural immunohistochemistry using labeled Fab'fragments of anti-hCG-alpha and anti-hCG-beta. Most reaction products were demonstrated in the rough endoplasmic reticulum (rER) and perinuclear spaces of syncytiotrophoblastic giant cells ( STGC ) occurring in embryonal carcinomas and in syncytial cells observed in choriocarcinomas and in normal placenta. The rER of placental and choriocarcinomatous syncytial cells was highly developed and invariably showed a positive reaction. However, the rER of STGCs varied both with regard to its degree of development and its immunoreactivity with hCG. Localization of hCG in the Golgi apparatus and in cytoplasmic granules was indefinite. Mononuclear cells reacting positively with anti-hCG-alpha or -beta were also demonstrated. Cytotrophoblast-like cells which failed to react with anti-hCG-alpha or -beta were noted adjacent to sTGCs and the significance of these cells is discussed.

A human gestational uterine choriocarcinoma cell line (NJG) was established in vitro. The NJG cell line had been subcultured more than 73 times over 7 years. The cells consisted mainly of Langhans-like cells, while multinucleated cells were occasionally seen. The cells grew in a monolayered sheet, showing a tendency to pile up, with the population doubling in 80 hrs. Electron-microscopically, desmosomes were characteristically observed, which suggested that the cultured cells were of epithelial origin. Chromosomal analysis revealed aneuploidy with a hypertriploid mode and 4 marker chromosomes. Immunocyto- and-histochemical staining for tumor markers of the cultured cells and the transplanted tumors to nude mice showed close similarity. SP1 was occasionally demonstrated and PP5 was faintly stained only in the heterotransplanted tumors, although PP10 and PP12 were not demonstrable. HCG was localized not only in syncytial cells, but also in Langhans cells, and syncytial cells without hCG were also observed in the tumors. A single cell clone was also established from the original NJG cells by a limiting dilution method. The heterotransplanted tumor consisted of Langhans and syncytial cells, indicating that both cells originated from the same cell.