A critical analysis of tumor morphology and hormone treatments in the untreated and estrogen-treated responsive and refractory human prostatic carcinoma

Abstract

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.

Effect of Bcl‐2 overexpression in human prostate cancer cells in vitro and in vivo

“…The average volumes on the day 21 were 75.7 ± 27.5 mm 3 for LNCaP/bcl‐2 and 8.0 ± 5.4 mm 3 for LNCaP/control ( P = 0.02). By day 35, however, the size of the tumors in all the mice had reached similar sizes of 101.8 ± 34.8 mm 3 and 128.5 ± 14.7 mm, 3 for LNCaP/bcl‐2 and LNCaP/control, respectively ( Fig. 4).…”

“…Prostate cancers generally show androgen‐dependent growth and undergo regression in response to androgen ablation by castration. 1,2 However, this treatment generally remains palliative and most eventually recur 3 and present androgen‐independent growth capacity as well as resistance to other treatment modalities, like chemotherapy. 4–6 It is now widely accepted that apoptosis, a genetically programmed process of autonomous cell death, is the mechanism of this regression and recurrent tumors develop anti‐apoptotic mechanism.…”

Transcriptional regulation of bcl-2 by nuclear factor κB and its significance in prostate cancer

“…Hormone ablation therapy has been a major treatment for prostate cancer for many years (Westin and Bergh, 1998). Although 70% of patients initially respond to this treatment, it is essentially palliative because, with time, almost all tumors will progress to an androgen independent state that is rapidly fatal (Sinha et al, 1977). An understanding of the molecular mechanisms that control this progression from hormone dependent to hormone independent is a key factor in the eective treatment of prostate cancer.…”

Apoptosis: Inhibitor or Instigator of Carcinogenesis?

“…Increased bcl-2 expression has also been associated with the progression of prostate cancer from androgen-dependent to androgen-independent growth (97). McDonnell et al (98) have suggested that the acquisition of an androgen-independent phenotype may be due to increased expression of bcl-2 because the majority of androgen-dependent tumors exhibited undetectable levels of the bcl-2 protein whereas the majority of androgen-independent prostate cancers tested exhibited high levels of bcl-2.…”