This study was done to compare the ultrastructural features of prostatic cancer cells in both untreated and estrogen-treated responsive and refractory patients. Analysis of previously untreated and estrogen-treated carcinomas showed that the tumors possessed well-and poorly-differentiated acini, and invasive cells. Malignant acini contained numerous columnar (secretory) cells in untreated, but few in treated individuals. Two distinct types of basal cells were observed in untreated and treated acini: type I (light) and type I1 (dark) cells. In both untreated and treated tumors, type I cells were characterized by having round nuclei with many small aggregates of euchromatin, large nucleoli, and electronlucent nucleoplasm. The type I1 cells had highly pleomorphic nuclei, folded nuclear envelope-sometimes deficient in localized areas, euchromatin, many small aggregates of heterochromatin, large pleomorphic nucleoli, and relatively electron-opaque nucleoplasm. In some sections, both types of basal cells penetrated through the acinar basal lamina and became invasive. Prostatic carcinomas which were or subsequently became refractory to estrogens showed more abundant type 11 basal cells than responsive patients. It is postulated that the type I1 basal cells as well as some type I basal cells are endocrine unresponsive from the outset. Furthermore the tumor possesses a heterogeneous population of cancer cells. While androgen-dependent tumor cells such as columnar cells may be destroyed by endocrine therapy, these endocrine unresponsive cells continue to proliferate, metastasize, and kill the patient. Therefore, we suggest that patient with advanced prostatic carcinoma initially may be given endocrine therapy to reduce tumor burden caused by endocrine-sensitive cells. In addition, early treatment with chemotherapy or radiation may be used to destroy unresponsive endocrine-insensitive cells, before these cells lines have a chance to proliferate and to develop into refractory carcinoma.
