Repeated biopsies in evaluation of therapeutic effects in prostate carcinoma.

BACKGROUND: Apoptosis is one of the major events following total androgen blockade (TAB). The aim of this study was to determine the predictive value of some histological parameters including apoptosis and gene products which influence apoptosis, based on repeated biopsies taken from the same patients. METHODS: At the time of diagnosis by needle biopsy TNM stage, serum PSA, Gleason's grade, apoptotic and mitotic index, Ki67, p53, and bcl(2) expression were investigated in 60 prostate carcinoma patients. Antiandrogen therapy supplemented with surgical or chemical castration was administered. Serum PSA-test and needle biopsy were repeated 13-14 weeks after starting the therapy, simultaneously with determination of the apoptotic and mitotic index, Ki67, p53, and bcl(2) expression. RESULTS: Forty-seven patients were alive at the end of the study, 13 patients died. Decrease in mitotic, increase in apoptotic index predicted favourable long-term response to antiandrogen therapy. Lower Ki67 and (mutant) p53 expression in the first and also in the second biopsy pointed to favourable effect of antiandrogen treatment. Since the ratio between Ki67 and apoptotic index strongly decreased in the survivors upon therapy, changes in Ki67/apoptosis ratio is recommended as a histologically detectable predictive factor. bcl(2) expression did not show significant correlation with the outcome of the disease. CONCLUSIONS: Histological evaluation of mitotic and apoptotic index, Ki67, and p53 expression in repeated biopsies contributes to predicting the value of the actual treatment and may be useful to institute alterations in therapy.

Pyeloureteral junction stenosis and ureteral valve causing hydronephrosis.

A young female patient underwent ureteral resection and Hynes-Anderson pyeloureteroplasty because of pyeloureteral junction stenosis and a ureteral valve (UV), which caused hydronephrosis. Despite using ultrasonography and intravenous urography the ureteral valve was observed only on exploration. UV should be considered as a possible cause of upper urinary tract obstruction; retrograde urography can be essential.

Apoptosis, mitosis, p53, bcl(2), Ki-67 and clinical outcome in prostate carcinoma treated by androgen ablation.

A prospective study on 16 patients with advanced (stage III and IV) prostate cancer was carried out. TNM stage, general clinical status, serum PSA level, the histological type and Gleason's grade of the tumor were registered. Total androgen blockade or single-drug therapy (flutamide) was performed. On average, 4.81 months after the start of therapy rebiopsy, serum PSA determination and general clinical examination were performed. Histologic examination before and after treatment of HE-stained slides, as well as apop-tag reaction to show apoptotic cells, p53, bcl(2), and Ki-67 immunostaining. Clinical improvement manifested by regression or lack of progression was observed in 10 patients. Increase of the apoptotic index and decrease of the mitotic index was detected in these cases. Serum PSA level decreased in all patients except in 3 fatal cases. The 6 clinically nonresponders who died after the second biopsy did not show an increased apoptotic or decreased mitotic index. Ki-67 positivity correlated well with the mitotic activity. Mutant p53 expression was higher in patients in whom antiandrogen therapy was ineffective. The bcl(2) expression was a characteristic of the tumors of patients who later died. These results show that the degree of induction of apoptosis in prostate carcinoma by hormonal therapy varies from case to case. A given prostate cancer patient's response to therapy may be predicted by following apoptotic and mitotic activity, as well as Ki-67 and p53 expression in repeated biopsies.