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Interracial Comparative Study of Prostate Cancer in the United States, China, and Japan
352
BENIGN AND MALIGNANT NEOPLASMS OF PROSTATE
Editorial Comment: What about serum androgen levels in black men? The authors suggest that black men without prostate cancer have similar androgen levels to white men. However, PSA levels and densities were significantly higher in black men. Prior studies have indicated that there are major differences in the androgen receptor in black men that may lead to increased transcriptional activity. I believe that target organ mechanisms such as this, rather than circulating androgen levels, are responsible for the apparent increased androgenic response in black men. Patrick C. Walsh, M.D.
Interracial Comparative Study of Prostate Cancer in the United States, China, and Japan H. E. ZHAU,L.3. Zmo, B.-Q. CHENAND M. KOJIMA,Molecular Urology and Therapeutics Program, Department of Urology, University of Virginia Health Sciences Center, Charlottesuille, Virginia, Department of Pathology, Norman Bethune University of Medical Sciences, Changchun, Jilin and Departments of Urology, X&ng Hospital, Xian, China, and University of Kyoto, Kyoto, Japan J. Cell. Biochem., suppl., 28/29 182-186, 1997 The interracial differences of prostate cancer progression have long been documented; however, underlying molecular and cellular mechanisms remain obscure. This study focuses on the histupathologic, immunohistochemical, biochemical, and molecular characterization of prostate cancer tissues unselectively obtained from US, Chinese, and Japanese men. Histopathologic analyses indicate that 74.5% of the prostate cancers in Chinese patients were poorly differentiated, compared with 28.6 and 32.8% of the prostate cancers in US and Japanese men, respectively. These differences cannot be attributed to patient age, clinical stage of disease, or methods of tissue sampling. Furthermore, the high proportion of poorly differentiated prostate cancer tissues in the Chinese group was not related to the patients' access to medical service or their geographic origins within China. We found significantly higher levels of tumor angiogenesis (2- to 4-fold), serotonin (2- to 20-fold), and bombesin (7to 16-fold), but not chromogranin A, in tissue specimens obtained from Chinese prostate cancer patients compared with those from US and Japanese patients. We also found marked differences in p53 protein accumulation among various ethnic groups. The p53 protein was frequently detected in prostate cancer tissue specimens from Chinese (90.2%),but less frequently in US black (3.7%), US white (17.4%), and Japanese (7.1%) men. Further analysis of 31 prostate cancer tissues from Chinese men indicated that mutational changes in the p53 gene occurred between exons 5 and 8.
Editorial Comment: Of Chinese men with prostate cancer 75% present with poorly differentiated disease and W' have mutations in p53. Because the frequency of incidental autopsy cancer is similar around the world, the difference in the incidence of clinical prostate cancer must be explained by factors that are involved in disease promotion. These authors speculate that the lower incidence of clinical prostate cancer in China may be due to the lack of the multihits necessary for clinical prostate cancer development and that genetic or genetidepigenetic interactions may account for the rapid progression of a subset of Chinese patients with prostate cancer. Patrick C. Walsh. M.D.
Evidence of Independent Origin of Multiple Tumors From Patients With Prostate Cancer L. CHENC,S.-Y. SONG,T. G. PRETLOW, F. W. ABDUL-KARIM, H.-J. KUNG,D. V. DAWSON, W . 3 . PARK, Y.-W. MOON,M.-L. TSAI,W. M. LINEHAN,M. R. EMMERT-BUCK, L. A. LIO~TA AND Z. ZHUANG, Departments of Microbiology and Molecular Biology, and Epidemiology and Biostatistics, Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, and Urologic Oncology Branch and Laboratory of Pathology, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland J . Natl. Cancer Inst., 90: 233-237, 1998 Background: In men with prostate cancer, the gland usually contains two or more widely separate tumors. A critical issue of prostatic carcinogenesis is whether these multiple tumors are independent in origin. Molecular analysis of microsatellite (i.e., highly repeated, short nucleotide sequences) alterations in the DNA from separate tumors in the same prostate can be used to determine whether or not these separate tumors arise independently. Methods: Four microsatellite polymorphic markers (D8S133, D8S136, and D85137, for a putative tumor suppressor gene on chromosome 8p, and D17S855, for the BRCAl gene on chromosome 17q) were used to examine the pattern of allelic loss in prostate cancer from 19 patients who had two or more distantly separate tumors (i.e., located on contralateral sides or separated by at least half the anterior-posterior diameter of the prostate). Forty distantly separate tumors were microdissected, DNA samples were prepared from formalin-fixed, paraffin-embedded wholemount prostate tissue section, and the
BENIGN AND MALIGNANT NEOPLASMS OF PROSTATE
Editorial Comment: What about serum androgen levels in black men? The authors suggest that black men without prostate cancer have similar androgen levels to white men. However, PSA levels and densities were significantly higher in black men. Prior studies have indicated that there are major differences in the androgen receptor in black men that may lead to increased transcriptional activity. I believe that target organ mechanisms such as this, rather than circulating androgen levels, are responsible for the apparent increased androgenic response in black men. Patrick C. Walsh, M.D.
Interracial Comparative Study of Prostate Cancer in the United States, China, and Japan H. E. ZHAU,L.3. Zmo, B.-Q. CHENAND M. KOJIMA,Molecular Urology and Therapeutics Program, Department of Urology, University of Virginia Health Sciences Center, Charlottesuille, Virginia, Department of Pathology, Norman Bethune University of Medical Sciences, Changchun, Jilin and Departments of Urology, X&ng Hospital, Xian, China, and University of Kyoto, Kyoto, Japan J. Cell. Biochem., suppl., 28/29 182-186, 1997 The interracial differences of prostate cancer progression have long been documented; however, underlying molecular and cellular mechanisms remain obscure. This study focuses on the histupathologic, immunohistochemical, biochemical, and molecular characterization of prostate cancer tissues unselectively obtained from US, Chinese, and Japanese men. Histopathologic analyses indicate that 74.5% of the prostate cancers in Chinese patients were poorly differentiated, compared with 28.6 and 32.8% of the prostate cancers in US and Japanese men, respectively. These differences cannot be attributed to patient age, clinical stage of disease, or methods of tissue sampling. Furthermore, the high proportion of poorly differentiated prostate cancer tissues in the Chinese group was not related to the patients' access to medical service or their geographic origins within China. We found significantly higher levels of tumor angiogenesis (2- to 4-fold), serotonin (2- to 20-fold), and bombesin (7to 16-fold), but not chromogranin A, in tissue specimens obtained from Chinese prostate cancer patients compared with those from US and Japanese patients. We also found marked differences in p53 protein accumulation among various ethnic groups. The p53 protein was frequently detected in prostate cancer tissue specimens from Chinese (90.2%),but less frequently in US black (3.7%), US white (17.4%), and Japanese (7.1%) men. Further analysis of 31 prostate cancer tissues from Chinese men indicated that mutational changes in the p53 gene occurred between exons 5 and 8.
Editorial Comment: Of Chinese men with prostate cancer 75% present with poorly differentiated disease and W' have mutations in p53. Because the frequency of incidental autopsy cancer is similar around the world, the difference in the incidence of clinical prostate cancer must be explained by factors that are involved in disease promotion. These authors speculate that the lower incidence of clinical prostate cancer in China may be due to the lack of the multihits necessary for clinical prostate cancer development and that genetic or genetidepigenetic interactions may account for the rapid progression of a subset of Chinese patients with prostate cancer. Patrick C. Walsh. M.D.
Evidence of Independent Origin of Multiple Tumors From Patients With Prostate Cancer L. CHENC,S.-Y. SONG,T. G. PRETLOW, F. W. ABDUL-KARIM, H.-J. KUNG,D. V. DAWSON, W . 3 . PARK, Y.-W. MOON,M.-L. TSAI,W. M. LINEHAN,M. R. EMMERT-BUCK, L. A. LIO~TA AND Z. ZHUANG, Departments of Microbiology and Molecular Biology, and Epidemiology and Biostatistics, Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, and Urologic Oncology Branch and Laboratory of Pathology, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland J . Natl. Cancer Inst., 90: 233-237, 1998 Background: In men with prostate cancer, the gland usually contains two or more widely separate tumors. A critical issue of prostatic carcinogenesis is whether these multiple tumors are independent in origin. Molecular analysis of microsatellite (i.e., highly repeated, short nucleotide sequences) alterations in the DNA from separate tumors in the same prostate can be used to determine whether or not these separate tumors arise independently. Methods: Four microsatellite polymorphic markers (D8S133, D8S136, and D85137, for a putative tumor suppressor gene on chromosome 8p, and D17S855, for the BRCAl gene on chromosome 17q) were used to examine the pattern of allelic loss in prostate cancer from 19 patients who had two or more distantly separate tumors (i.e., located on contralateral sides or separated by at least half the anterior-posterior diameter of the prostate). Forty distantly separate tumors were microdissected, DNA samples were prepared from formalin-fixed, paraffin-embedded wholemount prostate tissue section, and the