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.
Szende
B
B
1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. bszende@korb1.sote.hu
Romics
I
I
Minik
K
K
Szabó
J
J
Torda
I
I
Lovász
S
S
Szomor
L
L
Tóth
L
L
Bély
M
M
Kerényi
T
T
Bartók
K
K
Végh
A
A
D000367:Age Factors; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001706:Biopsy; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008940:Mitotic Index; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D017430:Prostate-Specific Antigen