UROLOGICAL SURVEY
Investigative urology
Immune mechanisms in bacillus Calmette-Guerin immunotherapy for superficial bladder cancer
Böhle A., Brandau S
From the HELIOS Agnes Karll Hospital (AB), Bad Schwartau and Division of Immunotherapy, Department of Immunology, Research Center Borstel (SB), Borstel, Germany
J Urol. 2003; 170: 964-9
PURPOSE: Of all medical disciplines it is exclusively in urology in which immunotherapy for cancer has an established position today with intravesical bacillus Calmette-Guerin (BCG) against superficial bladder carcinoma recurrences. BCG is regarded as the most successful immunotherapy to date. However, the mode of action has not yet been fully elucidated. We provide a thorough overview of this complex field of research.
MATERIALS AND METHODS: Rather than simply reporting all experimental data available for better understanding the involved immune mechanisms, we chose to provide comprehensively only information supported by several independent pathways of evidence.
RESULTS: Major findings made during the last few years include systematic analyses of patient material, detailed in vitro studies and investigations in animal models, which have led to a substantially greater understanding of the mechanisms involved.
CONCLUSIONS: The efficacy of BCG is based on a complex and long lasting local immune activation. The bladder as a confined compartment, in which high local concentrations of the immunotherapy agent and effective recruitment of immune cells can be achieved, serves as an ideal target organ for this type of immunotherapy approach.
Editorial Comment
Intravesical BCG against superficial bladder carcinoma recurrences is regarded as the most successful immunotherapy to date. However, the mode of action has not been fully elucidated yet. Since the immuno-activating properties of BCG were discovered, investigations have been carried out to ascertain the functional mechanism. All investigations to date have shown that not one single functional mechanism, but a whole series of immunological phenomena are involved.
Doctors Boehle and Brandau, world leading researchers on BCG in superficial bladder carcinoma, present in this article the most recent knowledge on this form of immunotherapy. They describe the major findings made during the last few years when systematic analyses of patient material, detailed in vitro studies and investigations on animal models have led to a substantially greater understanding of the mechanisms involved. This review explains why BCG therapy is currently considered the most successful immunotherapy of solid tumors, and therefore, must be read by every urologist interested in bladder cancer.
Dr. Francisco J.B. Sampaio
Full-Professor and Chief, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil
Racial differences in androgen receptor protein expression in men with clinically localized prostate cancer
Gaston KE, Kim D, Singh S, Ford OH 3rd, Mohler JL
From the Departments of Surgery and Pathology and Laboratory Medicine, and University of North Carolina-Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA
J Urol. 2003; 170: 990-3
PURPOSE: Black American men experience disproportionate mortality from prostate cancer (CaP) compared with white American men. Differences in outcome may stem from differences within the androgen axis. Since serum testosterone levels appear to be similar by race in men with CaP, we measured and compared androgen receptor (AR) protein expression in malignant and benign prostate tissue from black and white men who underwent radical prostatectomy for clinically localized CaP.
MATERIALS AND METHODS: Archived radical prostatectomy specimens obtained from 25 white and 25 black men had AR protein antigen retrieved and immunostained. AR protein expression from CaP and benign tissue was assessed by 2 methods. Automated digital color video image analysis was used to measure the percent area immunostained for AR protein and the intensity of expression (mean optical density). Visual scoring was performed to compare results with automated values.
RESULTS: In black compared with white men malignant nuclei were 27% more likely to immunostain for AR (p = 0.005) and in immunopositive nuclei AR protein expression was 81% greater (p = 0.002). Visual scoring of malignant nuclei revealed that AR immunostaining was significantly increased in black vs white men (171 ± 40 vs 149 ± 37, p = 0.048). In immunopositive benign nuclei AR protein expression was 22% greater in black than in white men (p = 0.027). Visual scoring of benign nuclei revealed 20% increased immunostaining in black vs white men, although this difference did not attain statistical significance (p = 0.065). Racial differences in AR protein expression were not explained by age, pathological grade or stage, although serum prostate specific antigen levels were higher in black men (9.7 ± 7.5 vs 15.5 ± 12.2 ng/ml, p = 0.049).
CONCLUSIONS: AR protein expression was 22% higher in the benign prostate and 81% higher in the CaP of black African compared with white men. CaP may occur at a younger age and progress more rapidly in black than in white men due to racial differences in androgenic stimulation of the prostate.
Editorial Comment
Although some controversies still exist, data on age adjusted deaths from CaP obtained from the Surveillance, Epidemiology, and End Results database from 1990 to 1998 in the USA revealed that Black American men have 2.3 times greater mortality from CaP than white American men. Previous works demonstrated that Black men are more frequently diagnosed with higher tumor volume, more advanced tumor stage, higher Gleason grade and higher prostate specific antigen (PSA) levels than white men are. The reasons for such findings are still not well understood.
This is the first study measuring and comparing androgen receptor (AR) protein expression in malignant and benign prostate tissue from black and white men who underwent radical prostatectomy for clinically localized CaP. The authors found that AR protein expression was 22% higher in the benign prostate and 81% higher in the CaP of black compared with white American men. Based on these findings, the authors speculated that CaP might occur at a younger age and progress more rapidly in black than in white men due to racial differences in androgenic stimulation of the prostate.
Dr. Francisco J.B. Sampaio
Full-Professor and Chief, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil
Publication Dates
-
Publication in this collection
12 Mar 2004 -
Date of issue
Aug 2003
