Potential therapeutic and diagnostic applications of the growth of testicular cancer in soft agar.

Sixteen histologically documented testicular cancer specimens obtained at diagnostic procedures following induction chemotherapy with cis-platinum containing regimens were cloned in soft agar. Seven (44%) of the specimens cultured formed colonies with a mean cloning efficiency of .021%. Colony formation was observed with all the common histologic subtypes of testicular cancer (seminoma, embryonal carcinoma, choriocarcinoma and mixed tumors). In vitro drug sensitivity tests were performed using cis-platinum, vinblastine and VP-16. Three of four specimens demonstrated a decrease in colony formation to less than 50% of controls after a 1 h exposure to VP-16 at 300 micrograms/ml. Two of these patients had a response to treatment with a VP-16 based salvage regimen. Immunoperoxidase staining of the colonies for alpha feto protein and human chorionic gonadotropin were correlated with the serum levels of these tumor markers determined at the time the specimen was obtained. In three instances the same markers were elevated in the serum as detected within cells which formed the colonies; however, in two other cases the marker(s) that was elevated in the serum was not expressed in the colonies. In one case a biopsy of a residual retroperitoneal mass following chemotherapy histologically was a teratoma, but it formed colonies in the assay which stained positive for alpha feto protein. This patient subsequently developed an elevated serum alpha feto protein. These studies have demonstrated that (a) testicular cancer can be cloned directly in soft agar; (b) a heterogeneous tumor cell population exists in metastatic testicular cancer specimens; and (c) a dose response exists for VP-16 in relapsed testicular cancer which suggests that increasing the dose of VP-16 may be clinically beneficial.