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Expression of Cyclooxygenase-1 and Cyclooxygenase-2 in the Human Prostate
BENIGN PROSTATIC HYPERPLASIA
Expression of Cyclooxygenase-1 and Cyclooxygenase-2 in the Human Prostate A. Kirschenbaum, A. P. Klausner, R. Lee, P. Unger, S. Yao, X. H. Liu and A. C. Levine, Department of Urology, Mount Sinai School of Medicine, New York, New York Urology, 56: 671– 676, 2000 Objectives: To determine the cell-specific expression of the two major isoforms of cyclooxygenase (COX-1 and COX-2) in human noncancerous and cancerous prostatic tissues. Methods: Thirty-one specimens of prostate carcinoma (CaP) and 10 specimens of benign prostatic hyperplasia (BPH) were stained with mouse antihuman COX-1 and COX-2 monoclonal antibodies. The stained specimens were analyzed both descriptively and in a semiquantitative manner by assigning an immunoreactive intensity score (0 to 4). The averaged results were compared for different histologic tissue types, including luminal and basal epithelium of BPH, the peripheral zone, high-grade prostatic intraepithelial neoplasia (PIN), and CaP of varying Gleason grades. Results: COX-1 expression in noncancerous prostatic tissue was seen predominantly in the basal epithelial cells of BPH (90% positive staining). COX-1 expression was minimal in noncancerous luminal epithelial cells (0% to 10%) but was upregulated in CaP (63% of CaP specimens). Strong COX-2 expression was demonstrated in the smooth muscle cells of the prostate. COX-2 was also expressed in the basal epithelial cells (60% BPH, 94% peripheral zone, 75% PIN). Luminal epithelial cells derived from BPH, the peripheral zone, and PIN expressed COX-2 in 0%, 26%, and 86% of samples, respectively. COX-2 expression in CaP was intense and uniform, with 87% of samples demonstrating immunoreactivity. Conclusions: The results of the present study indicate that expression of both COX-1 and COX-2 in human CaP is increased. COX-2 expression is also increased in the basal and luminal epithelial cells of PIN. These data indicate that COX-1 and COX-2 (and/or their prostatglandin products) may play a role in the malignant transformation of the prostate. Editorial Comment: The role of acute and chronic inflammation as well as microbial activities in prostate has been the subject of recent investigation. Moreover, the recognition that these processes can lead to malignancies in other organ systems, eg Helicobacter pylori is a risk factor for gastric cancer and gastric lymphoma, makes the prostate a reasonable area to explore. In addition, recent data suggest that in the Medical Therapy of Prostatic Symptoms study men who had inflammation on pretreatment biopsy were more likely to have progression of disease. The study by Konig et al analyzes the role of chemokines (RANTES,IL-8), chemotaxin receptors (CXCR-3, CCR-5), matrix metalloproteinases, TL receptors and inducible COX-2 in the development and maintenance of benign and malignant prostate cancer. The data suggest that BPH and prostate cancer have significant differences in expression of these various inflammatory chemokines. For example in BPH there is strong expression for TL receptors, 4, 5, 7 and 9. In contrast, prostate cancer has high expression for TL receptors 1, 2 and 3. In addition, there is differential expression with regard to COX-2, IL-6 and IL-8 expression. In the study by Kirschenbaum et al COX-1 and COX-2 expression was increased in human prostate cancer. It is interesting that COX-2 expression was increased in the basal and luminal epithelial cells of PIN. What is the clinical relevance of these findings? Clearly, targets directed at specific chemokines could be therapeutic alternatives, ie COX-2. However, enthusiasm should be tempered by clinical studies with respect to efficacy and safety. Exciting new studies using COX-2 inhibitors in genitourinary malignancies have been halted because of safety concerns regarding these agents. Nevertheless, these basic science findings will be the nidus for future clinical studies in prostate disease. Steven A. Kaplan, M.D.
Prospective Randomized Controlled Trial Comparing Plasmakinetic Vaporesection and Conventional Transurethral Resection of the Prostate B. T. Fung, S. K. Li, C. F. Yu, B. E. Lau and S. S. Hou, Division of Urology, Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong SAR, China Asian J Surg 28: 24 –28, 2005 Permission to Publish Abstract Not Granted Editorial Comment: During the last 20 years we have been inundated with new treatments for benign prostatic hyperplasia, each with great fanfare. With time many of these treatments have been discarded. What remains clear is that 3 therapeutic regimens have evolved—medical, minimally invasive (transurethral microwave thermotherapy, transurethral needle ablation of the prostate, interstitial laser coagulation), and transurethral prostatectomy (TURP) and/or one of its modifications. There is virtual unanimity that the most effective method to alleviate lower
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Expression of Cyclooxygenase-1 and Cyclooxygenase-2 in the Human Prostate A. Kirschenbaum, A. P. Klausner, R. Lee, P. Unger, S. Yao, X. H. Liu and A. C. Levine, Department of Urology, Mount Sinai School of Medicine, New York, New York Urology, 56: 671– 676, 2000 Objectives: To determine the cell-specific expression of the two major isoforms of cyclooxygenase (COX-1 and COX-2) in human noncancerous and cancerous prostatic tissues. Methods: Thirty-one specimens of prostate carcinoma (CaP) and 10 specimens of benign prostatic hyperplasia (BPH) were stained with mouse antihuman COX-1 and COX-2 monoclonal antibodies. The stained specimens were analyzed both descriptively and in a semiquantitative manner by assigning an immunoreactive intensity score (0 to 4). The averaged results were compared for different histologic tissue types, including luminal and basal epithelium of BPH, the peripheral zone, high-grade prostatic intraepithelial neoplasia (PIN), and CaP of varying Gleason grades. Results: COX-1 expression in noncancerous prostatic tissue was seen predominantly in the basal epithelial cells of BPH (90% positive staining). COX-1 expression was minimal in noncancerous luminal epithelial cells (0% to 10%) but was upregulated in CaP (63% of CaP specimens). Strong COX-2 expression was demonstrated in the smooth muscle cells of the prostate. COX-2 was also expressed in the basal epithelial cells (60% BPH, 94% peripheral zone, 75% PIN). Luminal epithelial cells derived from BPH, the peripheral zone, and PIN expressed COX-2 in 0%, 26%, and 86% of samples, respectively. COX-2 expression in CaP was intense and uniform, with 87% of samples demonstrating immunoreactivity. Conclusions: The results of the present study indicate that expression of both COX-1 and COX-2 in human CaP is increased. COX-2 expression is also increased in the basal and luminal epithelial cells of PIN. These data indicate that COX-1 and COX-2 (and/or their prostatglandin products) may play a role in the malignant transformation of the prostate. Editorial Comment: The role of acute and chronic inflammation as well as microbial activities in prostate has been the subject of recent investigation. Moreover, the recognition that these processes can lead to malignancies in other organ systems, eg Helicobacter pylori is a risk factor for gastric cancer and gastric lymphoma, makes the prostate a reasonable area to explore. In addition, recent data suggest that in the Medical Therapy of Prostatic Symptoms study men who had inflammation on pretreatment biopsy were more likely to have progression of disease. The study by Konig et al analyzes the role of chemokines (RANTES,IL-8), chemotaxin receptors (CXCR-3, CCR-5), matrix metalloproteinases, TL receptors and inducible COX-2 in the development and maintenance of benign and malignant prostate cancer. The data suggest that BPH and prostate cancer have significant differences in expression of these various inflammatory chemokines. For example in BPH there is strong expression for TL receptors, 4, 5, 7 and 9. In contrast, prostate cancer has high expression for TL receptors 1, 2 and 3. In addition, there is differential expression with regard to COX-2, IL-6 and IL-8 expression. In the study by Kirschenbaum et al COX-1 and COX-2 expression was increased in human prostate cancer. It is interesting that COX-2 expression was increased in the basal and luminal epithelial cells of PIN. What is the clinical relevance of these findings? Clearly, targets directed at specific chemokines could be therapeutic alternatives, ie COX-2. However, enthusiasm should be tempered by clinical studies with respect to efficacy and safety. Exciting new studies using COX-2 inhibitors in genitourinary malignancies have been halted because of safety concerns regarding these agents. Nevertheless, these basic science findings will be the nidus for future clinical studies in prostate disease. Steven A. Kaplan, M.D.
Prospective Randomized Controlled Trial Comparing Plasmakinetic Vaporesection and Conventional Transurethral Resection of the Prostate B. T. Fung, S. K. Li, C. F. Yu, B. E. Lau and S. S. Hou, Division of Urology, Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong SAR, China Asian J Surg 28: 24 –28, 2005 Permission to Publish Abstract Not Granted Editorial Comment: During the last 20 years we have been inundated with new treatments for benign prostatic hyperplasia, each with great fanfare. With time many of these treatments have been discarded. What remains clear is that 3 therapeutic regimens have evolved—medical, minimally invasive (transurethral microwave thermotherapy, transurethral needle ablation of the prostate, interstitial laser coagulation), and transurethral prostatectomy (TURP) and/or one of its modifications. There is virtual unanimity that the most effective method to alleviate lower
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