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.
Patients treated with a 5.0‐mg daily dose of diethylstilbestrol (DES) had an increased incidence of fatal and non‐fatal cardiovascular disease when compared to placebo in all stages of prostatic cancer (p < 0.025). The pretreatment cardiovascular status of estrogen‐treated patients was generally better than those treated with placebo. Therapy with DES 5.0 mg did not increase survival of Stage III or IV patients significantly when compared to placebo. The decrease in cancer mortality associated with the 5.0‐mg dose of DES was offset by an increase in deaths from cardiovascular causes. Early endocrine treatment of patients with asymptomatic Stage III carcinoma is not indicated. Endocrine therapy should be started early only in Stage IV patients. When DES is preferred, it should be administered in a dose lower than 5.0 mg. Complications of estrogen therapy may be due to an increased incidence of thromboembolism.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.