- Email: [email protected]
Ethnicity and its significance in the pathobiology of prostatic carcinoma in Southern Israel
Urologic Oncology: Seminars and Original Investigations 26 (2008) 31–36
Original article
Ethnicity and its significance in the pathobiology of prostatic carcinoma in Southern Israel Netta Sion-Vardy, M.D.a, Zvia Priel-Cohen, M.Sc.a, Wilmosh Mermershtain, M.D.b, Endre Neulander, M.D.c, Daniel Benharroch, M.D.a,* a
Institute of Pathology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel Institute of Oncology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel c Department of Urology, Sorooka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel b
Received 22 September 2006; received in revised form 17 January 2007; accepted 18 January 2007
Abstract Background: Several studies have noted ethnic differences in the natural history of prostatic carcinoma. Southern Israel has been regarded as a melting pot and, perhaps more than the rest of the country, has encouraged the ingathering of immigrants from several countries, as well as a large Bedouin community. Objectives: In an attempt to determine any differences that may exist in population groups in Israel, we have examined clinical and biologic markers in patients diagnosed with prostatic cancer in Southern Israel in 1996 –2000. We wanted to demonstrate differences in the incidence and features of prostate carcinoma among the population groups in Southern Israel, and to evaluate their possible biologic significance. Methods: Clinical parameter features, including the ethnicity origin of patients with prostatic adenocarcinoma, were reviewed in a cohort of 189 patients seen between 1996 and 2000. Tissue sections from specimens in a subset of 40 of these patients who had undergone prostatectomy were studied by immunohistochemistry for TP53, Bcl-2, and chromogranin A using the ABC peroxidase method. These markers were chosen because of their suggested impact on the biology of this tumor. Clinical correlations were examined. Results: We confirm the presence of ethnic differences in the features of prostatic adenocarcinoma in our geographic area. Notably, patients of North African origin were treated surgically at a younger age than immigrants from East Europe. Higher total prostate-specific antigen levels and more robust tumor cell Bcl-2 expression were detected in the East European patients. The number of Bedouin subjects in our cohort of patients with prostatic cancer was much more limited than expected. No immigrants from Ethiopia were included in our study diagnosed with prostate carcinoma during this period. Conclusions: The proportion of patients of European, especially East European, origin was relatively high among the cohort of 189. Their older age and the lower proportion of subjects that underwent surgery, together with the tendency toward higher total prostate-specific antigen levels and higher Bcl-2 expression, suggest that this ethnic group may not differ significantly from the African-American group in the United States. The low representation of Bedouin and absence of Ethiopian immigrants among our patients with prostate cancer may point to a genuinely low incidence or it may be related to inadequate medical supervision in these population groups. © 2008 Elsevier Inc. All rights reserved. Keywords: Prostate carcinoma; Ethnicity; Prostatectomy
1. Introduction Prostate adenocarcinoma is a major health problem, and a significant cause of morbidity and mortality in men worldwide [1,2]. Race and a family history are two accepted risk factors for this disease. * Corresponding author. Tel.: ⫹972-8-6400920; fax: ⫹972-8-6232770. E-mail address: [email protected] (D. Benharroch). 1078-1439/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.urolonc.2007.01.023
There are marked ethnic and racial differences in the epidemiology of prostate carcinoma. African-Americans have a higher incidence and mortality rate than both white non-Hispanic and Hispanics. Differences in the behavior of prostate cancer have also been detected among other ethnic groups such as Filipino, Japanese, and Hawaiians in the United States [3]. Model systems are required to investigate and understand the prostate cancer biologic behavior in different ethnic groups. An understanding of the underlying
32
N. Sion-Vardy et al. / Urologic Oncology: Seminars and Original Investigations 26 (2008) 31–36
biologic mechanisms that influence the progress of prostate cancer may eventually lead to the development of more efficient treatment. The population of the Beer-Sheva region in Southern Israel (Negev) is composed of several different ethnic groups [4]. Of these are Israel-born individuals, immigrants from Europe, considered together with immigrants from the United States, because of their common Ashkenazi origin, immigrants from North Africa and from Asia (Sepharadi Jews) [5,6]. Within the Ashkenazi Jews, immigrants from the former Union of Soviet Socialist Republics are set apart because of specific cultural and medical characteristics. The population of the Beer-Sheva area also includes a large number of Bedouins, who make up about 20% of this population. A small fraction of this population, about 4%, represents the newly arrived group of Ethiopian Jews. In the current study, we examine the clinical (age and prostate-specific antigen [PSA] level), biologic (Gleason score), and molecular parameters of prostate cancer (TP53, Bcl-2, and chromogranin A). The latter were chosen for their relevance to the progression of prostate cancer [7–10]. Confirmation of the role of ethnicity in prostate adenocarcinoma, as well as the detection of possible clues as to the cause of the differences, was set as our objective. The study aimed at showing peculiar associations between prostate adenocarcinoma and the ethnic or geographic origin of the patients, which may disclose clues as to the pathogenesis of this malignant tumor.
2. Materials and methods We retrieved the details of 189 patients diagnosed with prostate adenocarcinoma between the years 1996 and 2000 in the computerized files of the Pathology Department of the Soroka University Medical Center. This cohort represents the basis of our study. The clinicopathologic data (age, total PSA levels, and Gleason score) were obtained from the charts of the patients. The data on country of birth and ethnic group were collected from the Israeli Statistic Annual (No. 50, 1999). A subset of 40 patients had undergone prostatectomy. Immunohistochemical studies were performed on 40 of these patients who had undergone prostatectomy (radical in 37 and retropubic in 3). We retrieved the formalin-fixed, paraffin-embedded samples from these 40 prostatectomies, reviewed the histologic findings, and selected one representative slide of each case for immunohistochemical study. The immunohistochemical study was performed on 5-m paraffin sections with the ABC peroxidase kit from Vector Laboratories (Burlingame, CA). Sections were stained on polylysine-coated slides by incubation with the monoclonal antibody DO-7 (Dako, Glostrup, Denmark), which recognizes both mutant as well as wild-type TP53 protein, followed by a biotinylated anti-mouse immuno-
globulin. We used 3,3=-diaminobenzidine-chromogen as a substrate and followed with hematoxylin counterstain. TP53 and the Bcl-2 antibodies were purchased from Dako, and chromogranin A was obtained from Boeringer Manheim (Manheim, Germany). Sections were obtained from an undifferentiated rhabdomyosarcoma, a lymph node with grade I follicular lymphoma, and a gastric neuroendocrine carcinoma for TP53, Bcl-2, and chromogranin A, respectively. Omission of the primary antibody was used as a negative control. The stains were regarded as positive for TP53 if more than 10% of the cell nuclei were positively stained in at least 5 high-power fields. The stains were regarded as positive for Bcl-2 if the cytoplasm showed moderate-to-strong staining in more than 2% of the cells. Chromogranin was regarded as positive when at least 2% of the glands were positively stained [11]. We put special emphasis on the comparison of patients born in East Europe and North Africa who constitute the 2 largest Jewish communities in the Beer-Sheva area. Because the 2 largest Jewish communities in our area, as well as in the subset of patients with prostatectomy, originate from East Europe and North Africa, we paid special attention to a comparison between these 2 groups.
3. Results Of the basic cohort of 189 patients diagnosed with prostate adenocarcinoma, 58% (n ⫽ 103) were immigrants from Europe and America, and 35% (n ⫽ 57) from Asia and Africa. The percentage of the European-American ethnic group in our cohort was higher than their percentage in the population of Southern Israel. Only 6% (n ⫽ 12) were Israel-born patients, a low incidence as compared with their proportion in the population. The incidence of patients from Asia was also very low. The proportion of immigrants from Africa, nearly all of whom were from North Africa, with prostate adenocarcinoma, is more balanced with regard to their percentage in the population (Fig. 1). Only 5 Bedouin (3%) subjects were diagnosed as having prostate adenocarcinoma, a figure that is much lower than their percentage in the population of Southern Israel (22%). There were no patients of Ethiopian origin. Because the East European and North African communities are the largest in our area, we compared their morbidity and mortality with prostate adenocarcinoma. Of the 189 men, 96 were of East European origin, and 54 men of North African origin had a biopsy diagnosis of prostate adenocarcinoma. Of the North African patients, 18 (33.3%) underwent total prostatectomy, as compared to only 15 (15.6%) of the patients of East European origin (P ⫽ 0.012). A total of 29 patients had undergone prostatectomy at an age younger than 60; 6 of them (20.7%) were of North African origin (Fig. 1). The Gleason scores of the North African group were higher than those of the East European
N. Sion-Vardy et al. / Urologic Oncology: Seminars and Original Investigations 26 (2008) 31–36
33
Fig. 1. Origin of patients with prostate cancer in comparison to the origin of the general Jewish population in the Beer-Sheva region. (Color version of figure is available online.)
group (Fig. 2). More patients in the East European cohort had blood PSA values higher than 10 ng/ml than in the North African group (Fig. 3). In the 40 patients who had undergone prostatectomy, we studied the molecular markers Bcl-2, TP53, and chromogranin A. The expression of Bcl-2 tended to be higher in the East European group than in the North African group (Fig. 4). No significant differences were seen in the expression of chromogranin A and TP53 in the different ethnic groups.
4. Discussion Prostate carcinoma is the most common malignancy in men older than the age of 60. It is the second leading cause of cancer-related deaths among men in the Western world. Several ethnic and racial differences have been reported in prostate carcinoma. African-Americans have a higher incidence of the disease than Caucasians, and have a more aggressive tumor behavior. The incidence and mortality rates from prostate cancer are lower among Asians, Hawai-
Fig. 2. Gleason score by origin. (Color version of figure is available online.)
34
N. Sion-Vardy et al. / Urologic Oncology: Seminars and Original Investigations 26 (2008) 31–36
Fig. 3. Blood PSA levels by origin. (Color version of figure is available online.)
ians, Hispanic, and Native Americans than in AfricanAmericans and Caucasians [3,12]. The reasons for the differences are not clear. One of the suggested explanations is the difference in androgenic environment within the prostatic tissue in the different ethnic/racial groups [13]. There is considerable controversy as to whether race is an independent predictor of disease-free survival in patients with prostate cancer presenting with the same stage and similar treatment. Multiple variable analyses of race as a predictor of disease-free survival in patients with radical
prostatectomy have shown inconsistent findings [14 –16], which is not unexpected. If prostate adenocarcinoma is usually diagnosed at a more advanced stage in a particular group, this may indicate a strong association between the population group and a poor outcome malignancy. On the other hand, this assumption may not be justified. Powell et al. [17] studied 791 patients who underwent radical prostatectomy, and concluded that early diagnosis and treatment significantly decreased the role of the race of the patients in outcome.
Fig. 4. Bcl-2 stain by origin. (Color version of figure is available online.)
N. Sion-Vardy et al. / Urologic Oncology: Seminars and Original Investigations 26 (2008) 31–36
In our study, we chose to investigate the expression of several clinical and biologic markers of prostate adenocarcinoma in the population of the Beer-Sheva area in view of the higher ethnic diversity in this region, as compared to that in Israel as a whole. There were no differences in the clinicopathologic features of prostate carcinoma in the various population groups apart from those found between the East European and North African groups. The North African patients with prostate adenocarcinoma tended to be diagnosed and treated surgically at a younger age than those of East European origin. The reason for the difference is not clear. The older age at diagnosis may have prevented some of the East European patients from being eligible for radical surgery. A study of extended cohorts of these 2 groups that would include environmental factors, such as viral, nutritional, alcohol consumption, and smoking habits, as well as genetic factors, would seem to be warranted. The unexpected paucity of Bedouin subjects in our study may signify a low incidence of prostate adenocarcinoma. However, it may suggest their low compliance to medical prostate examination. Surprisingly, no immigrants of Ethiopian origin were diagnosed with prostate adenocarcinoma, although the Ethiopian population may be considered a priori to have features in common with the African-American population in the United States. It is noteworthy that the rate of autopsy examination in the Ethiopian as well as Bedouin population is very low at our center. This result would prevent more objective evaluation of the true incidence of prostate adenocarcinoma [18]. Our figures probably represent a gross underestimation of prostate adenocarcinoma among the Ethiopian and Bedouin groups. The reason for their lack of representation in our cohort may be the result of a cultural behavior pattern that prevents them from seeking medical consultation regarding their genitourinary problems. Education on medical subjects, including prostate cancer and screening programs among the Ethiopian and Bedouin communities, should be considered. Regarding the biologic markers studied, we found that the patients from East Europe had a higher expression of Bcl-2 in their prostate tumors. Bcl-2 is an apoptosis-inhibiting factor protein that may enhance the stability of tumor to the radiotherapy in different populations [19]. Further studies evaluating the response of the different groups to radiotherapy are warranted. Higher values of TP53 are expressed in malignant tumors showing more aggressive behavior. No significant change of expression of this marker in prostate cancer was seen in the different ethnic groups in our study. Prostate carcinoma that escapes antiandrogenic treatment shows a higher expression of neuroendocrine features, including chromogranin A [9,10]. No significant immunostaining differences of chromogranin A were detected in the different ethnic groups in our study.
35
5. Conclusions We found ethnic differences in the clinical and biologic features of prostate adenocarcinoma in Southern Israel. There were more significant differences in the 2 largest Jewish population groups in South Israel. The patients of North African origin were diagnosed and treated at a younger age. A cultural difference in seeking help for genitourinary complaints may account for this finding. However, a genetic/familial difference is not excluded. No pathogenic clue regarding prostate adenocarcinoma was revealed in our study, but there were differences in the biologic characteristics of the tumor between the 2 largest population groups. It has been suggested that because these 2 groups originate from common ancestors [4], environmental factors such as cigarette smoking, viral infection, dietetic factors, or other chemical exposure may explain some of the differences.
References [1] Garnick MB, Fair WR. Prostate cancer: Emerging concepts. Part I. Ann Intern Med 1996;125:118 –25. [2] Jemal A, Tiwari RC, Murray T, et al. American Cancer Society. Cancer statistics, 2004. CA Cancer J Clin 2004;54:8 –29. [3] Brawley OW, Knopf K, Merrill R. The epidemiology of prostate cancer part I: Descriptive epidemiology. Semin Urol Oncol 1998;16: 187–92. [4] Davidovici B, Karakis I, Bourboulia D, et al. Seroepidemiology and molecular epidemiology of Kaposi’s sarcoma–Associated herpesvirus among Jewish population groups in Israel. J Natl Cancer Inst 2001; 93:194 –202. [5] Khouaja K, Ben Sorba N, Bouslama A, et al. An experience of individual and early diagnosis of prostate cancer in a Tunisian center. Prog Urol 2005;15:255–9. [6] Muir CS, Nectoux J, Straszewski J. The epidemiology of prostatic cancer. Geographical distribution and time-trends. Acta Oncol 1991; 30:133– 40. [7] Theodorescu D, Broder SR, Boyd JC, et al. p53, bcl-2 and retinoblastoma proteins as long-term prognostic markers in localized carcinoma of the prostate. J Urol 1997;158:131–7. [8] Zellweger T, Ninck C, Bloch M, et al. Expression patterns of potential therapeutic targets in prostate cancer. Int J Cancer 2005;113: 619 –28. [9] Quek ML, Daneshmand S, Rodrigo S, et al. Prognostic significance of neuroendocrine expression in lymph-node positive prostate cancer. Urology 2006;67:1247–52. [10] Wafa LA, Palmer J, Fazli L, et al. Comprehensive expression analysis of l-dopa decarboxylase and established neuroendocrine markers in neoadjuvant hormone-treated versus varying Gleason grade prostate tumors. Hum Pathol 2007;38:161–70. [11] Sion-Vardy N, Tzikinovsky A, Bolotyn A, et al. Augmented expression of chromogranin A and serotonin in peri-malignant benign prostate epithelium as compared to adenocarcinoma. Pathol Res Pract 2004;200:493–9. [12] Morton RA Jr. Racial differences in adenocarcinoma of the prostate in North American men. Urology 1994;44:637– 45. [13] Ross R, Bernstein L, Judd H, et al. Serum testosterone levels in healthy young black and white men. J Natl Cancer Inst 1986;76:45– 8. [14] Moul JW, Douglas TH, McCarthy WF, et al. Black race is an adverse prognostic factor for prostate cancer recurrence following radical
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prostatectomy in an equal access health care setting. J Urol 1996; 155:1667–73. [15] Freedland SJ, Jalkut M, Dorey F, et al. Race is not an independent predictor of biochemical recurrence after radical prostatectomy in an equal access medical center. Urology 2000;56:87–91. [16] Powell IJ, Dey J, Dudley A, et al. Disease-free survival difference between African Americans and whites after radical prostatectomy for local prostate cancer: A multivariable analysis. Urology 2002;59: 907–12.
[17] Powell IJ, Banerjee M, Bianco FJ, et al. The effect of race/ethnicity on prostate cancer treatment outcome is conditional: A review of Wayne State University data. J Urol 2004;171:1508 –12. [18] Soos G, Tsakiris I, Szanto J, et al. The prevalence of prostate carcinoma and its precursors in Hungary: An autopsy study. Eur Urol 2005;48:739 – 44. [19] Mackey TJ, Borkowski A, Amin P, et al. Bcl-2/bax ratio as a predictive marker for therapeutic response to radiotherapy in patients with prostate cancer. Urology 1998;52:1085–90.
Original article
Ethnicity and its significance in the pathobiology of prostatic carcinoma in Southern Israel Netta Sion-Vardy, M.D.a, Zvia Priel-Cohen, M.Sc.a, Wilmosh Mermershtain, M.D.b, Endre Neulander, M.D.c, Daniel Benharroch, M.D.a,* a
Institute of Pathology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel Institute of Oncology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel c Department of Urology, Sorooka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel b
Received 22 September 2006; received in revised form 17 January 2007; accepted 18 January 2007
Abstract Background: Several studies have noted ethnic differences in the natural history of prostatic carcinoma. Southern Israel has been regarded as a melting pot and, perhaps more than the rest of the country, has encouraged the ingathering of immigrants from several countries, as well as a large Bedouin community. Objectives: In an attempt to determine any differences that may exist in population groups in Israel, we have examined clinical and biologic markers in patients diagnosed with prostatic cancer in Southern Israel in 1996 –2000. We wanted to demonstrate differences in the incidence and features of prostate carcinoma among the population groups in Southern Israel, and to evaluate their possible biologic significance. Methods: Clinical parameter features, including the ethnicity origin of patients with prostatic adenocarcinoma, were reviewed in a cohort of 189 patients seen between 1996 and 2000. Tissue sections from specimens in a subset of 40 of these patients who had undergone prostatectomy were studied by immunohistochemistry for TP53, Bcl-2, and chromogranin A using the ABC peroxidase method. These markers were chosen because of their suggested impact on the biology of this tumor. Clinical correlations were examined. Results: We confirm the presence of ethnic differences in the features of prostatic adenocarcinoma in our geographic area. Notably, patients of North African origin were treated surgically at a younger age than immigrants from East Europe. Higher total prostate-specific antigen levels and more robust tumor cell Bcl-2 expression were detected in the East European patients. The number of Bedouin subjects in our cohort of patients with prostatic cancer was much more limited than expected. No immigrants from Ethiopia were included in our study diagnosed with prostate carcinoma during this period. Conclusions: The proportion of patients of European, especially East European, origin was relatively high among the cohort of 189. Their older age and the lower proportion of subjects that underwent surgery, together with the tendency toward higher total prostate-specific antigen levels and higher Bcl-2 expression, suggest that this ethnic group may not differ significantly from the African-American group in the United States. The low representation of Bedouin and absence of Ethiopian immigrants among our patients with prostate cancer may point to a genuinely low incidence or it may be related to inadequate medical supervision in these population groups. © 2008 Elsevier Inc. All rights reserved. Keywords: Prostate carcinoma; Ethnicity; Prostatectomy
1. Introduction Prostate adenocarcinoma is a major health problem, and a significant cause of morbidity and mortality in men worldwide [1,2]. Race and a family history are two accepted risk factors for this disease. * Corresponding author. Tel.: ⫹972-8-6400920; fax: ⫹972-8-6232770. E-mail address: [email protected] (D. Benharroch). 1078-1439/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.urolonc.2007.01.023
There are marked ethnic and racial differences in the epidemiology of prostate carcinoma. African-Americans have a higher incidence and mortality rate than both white non-Hispanic and Hispanics. Differences in the behavior of prostate cancer have also been detected among other ethnic groups such as Filipino, Japanese, and Hawaiians in the United States [3]. Model systems are required to investigate and understand the prostate cancer biologic behavior in different ethnic groups. An understanding of the underlying
32
N. Sion-Vardy et al. / Urologic Oncology: Seminars and Original Investigations 26 (2008) 31–36
biologic mechanisms that influence the progress of prostate cancer may eventually lead to the development of more efficient treatment. The population of the Beer-Sheva region in Southern Israel (Negev) is composed of several different ethnic groups [4]. Of these are Israel-born individuals, immigrants from Europe, considered together with immigrants from the United States, because of their common Ashkenazi origin, immigrants from North Africa and from Asia (Sepharadi Jews) [5,6]. Within the Ashkenazi Jews, immigrants from the former Union of Soviet Socialist Republics are set apart because of specific cultural and medical characteristics. The population of the Beer-Sheva area also includes a large number of Bedouins, who make up about 20% of this population. A small fraction of this population, about 4%, represents the newly arrived group of Ethiopian Jews. In the current study, we examine the clinical (age and prostate-specific antigen [PSA] level), biologic (Gleason score), and molecular parameters of prostate cancer (TP53, Bcl-2, and chromogranin A). The latter were chosen for their relevance to the progression of prostate cancer [7–10]. Confirmation of the role of ethnicity in prostate adenocarcinoma, as well as the detection of possible clues as to the cause of the differences, was set as our objective. The study aimed at showing peculiar associations between prostate adenocarcinoma and the ethnic or geographic origin of the patients, which may disclose clues as to the pathogenesis of this malignant tumor.
2. Materials and methods We retrieved the details of 189 patients diagnosed with prostate adenocarcinoma between the years 1996 and 2000 in the computerized files of the Pathology Department of the Soroka University Medical Center. This cohort represents the basis of our study. The clinicopathologic data (age, total PSA levels, and Gleason score) were obtained from the charts of the patients. The data on country of birth and ethnic group were collected from the Israeli Statistic Annual (No. 50, 1999). A subset of 40 patients had undergone prostatectomy. Immunohistochemical studies were performed on 40 of these patients who had undergone prostatectomy (radical in 37 and retropubic in 3). We retrieved the formalin-fixed, paraffin-embedded samples from these 40 prostatectomies, reviewed the histologic findings, and selected one representative slide of each case for immunohistochemical study. The immunohistochemical study was performed on 5-m paraffin sections with the ABC peroxidase kit from Vector Laboratories (Burlingame, CA). Sections were stained on polylysine-coated slides by incubation with the monoclonal antibody DO-7 (Dako, Glostrup, Denmark), which recognizes both mutant as well as wild-type TP53 protein, followed by a biotinylated anti-mouse immuno-
globulin. We used 3,3=-diaminobenzidine-chromogen as a substrate and followed with hematoxylin counterstain. TP53 and the Bcl-2 antibodies were purchased from Dako, and chromogranin A was obtained from Boeringer Manheim (Manheim, Germany). Sections were obtained from an undifferentiated rhabdomyosarcoma, a lymph node with grade I follicular lymphoma, and a gastric neuroendocrine carcinoma for TP53, Bcl-2, and chromogranin A, respectively. Omission of the primary antibody was used as a negative control. The stains were regarded as positive for TP53 if more than 10% of the cell nuclei were positively stained in at least 5 high-power fields. The stains were regarded as positive for Bcl-2 if the cytoplasm showed moderate-to-strong staining in more than 2% of the cells. Chromogranin was regarded as positive when at least 2% of the glands were positively stained [11]. We put special emphasis on the comparison of patients born in East Europe and North Africa who constitute the 2 largest Jewish communities in the Beer-Sheva area. Because the 2 largest Jewish communities in our area, as well as in the subset of patients with prostatectomy, originate from East Europe and North Africa, we paid special attention to a comparison between these 2 groups.
3. Results Of the basic cohort of 189 patients diagnosed with prostate adenocarcinoma, 58% (n ⫽ 103) were immigrants from Europe and America, and 35% (n ⫽ 57) from Asia and Africa. The percentage of the European-American ethnic group in our cohort was higher than their percentage in the population of Southern Israel. Only 6% (n ⫽ 12) were Israel-born patients, a low incidence as compared with their proportion in the population. The incidence of patients from Asia was also very low. The proportion of immigrants from Africa, nearly all of whom were from North Africa, with prostate adenocarcinoma, is more balanced with regard to their percentage in the population (Fig. 1). Only 5 Bedouin (3%) subjects were diagnosed as having prostate adenocarcinoma, a figure that is much lower than their percentage in the population of Southern Israel (22%). There were no patients of Ethiopian origin. Because the East European and North African communities are the largest in our area, we compared their morbidity and mortality with prostate adenocarcinoma. Of the 189 men, 96 were of East European origin, and 54 men of North African origin had a biopsy diagnosis of prostate adenocarcinoma. Of the North African patients, 18 (33.3%) underwent total prostatectomy, as compared to only 15 (15.6%) of the patients of East European origin (P ⫽ 0.012). A total of 29 patients had undergone prostatectomy at an age younger than 60; 6 of them (20.7%) were of North African origin (Fig. 1). The Gleason scores of the North African group were higher than those of the East European
N. Sion-Vardy et al. / Urologic Oncology: Seminars and Original Investigations 26 (2008) 31–36
33
Fig. 1. Origin of patients with prostate cancer in comparison to the origin of the general Jewish population in the Beer-Sheva region. (Color version of figure is available online.)
group (Fig. 2). More patients in the East European cohort had blood PSA values higher than 10 ng/ml than in the North African group (Fig. 3). In the 40 patients who had undergone prostatectomy, we studied the molecular markers Bcl-2, TP53, and chromogranin A. The expression of Bcl-2 tended to be higher in the East European group than in the North African group (Fig. 4). No significant differences were seen in the expression of chromogranin A and TP53 in the different ethnic groups.
4. Discussion Prostate carcinoma is the most common malignancy in men older than the age of 60. It is the second leading cause of cancer-related deaths among men in the Western world. Several ethnic and racial differences have been reported in prostate carcinoma. African-Americans have a higher incidence of the disease than Caucasians, and have a more aggressive tumor behavior. The incidence and mortality rates from prostate cancer are lower among Asians, Hawai-
Fig. 2. Gleason score by origin. (Color version of figure is available online.)
34
N. Sion-Vardy et al. / Urologic Oncology: Seminars and Original Investigations 26 (2008) 31–36
Fig. 3. Blood PSA levels by origin. (Color version of figure is available online.)
ians, Hispanic, and Native Americans than in AfricanAmericans and Caucasians [3,12]. The reasons for the differences are not clear. One of the suggested explanations is the difference in androgenic environment within the prostatic tissue in the different ethnic/racial groups [13]. There is considerable controversy as to whether race is an independent predictor of disease-free survival in patients with prostate cancer presenting with the same stage and similar treatment. Multiple variable analyses of race as a predictor of disease-free survival in patients with radical
prostatectomy have shown inconsistent findings [14 –16], which is not unexpected. If prostate adenocarcinoma is usually diagnosed at a more advanced stage in a particular group, this may indicate a strong association between the population group and a poor outcome malignancy. On the other hand, this assumption may not be justified. Powell et al. [17] studied 791 patients who underwent radical prostatectomy, and concluded that early diagnosis and treatment significantly decreased the role of the race of the patients in outcome.
Fig. 4. Bcl-2 stain by origin. (Color version of figure is available online.)
N. Sion-Vardy et al. / Urologic Oncology: Seminars and Original Investigations 26 (2008) 31–36
In our study, we chose to investigate the expression of several clinical and biologic markers of prostate adenocarcinoma in the population of the Beer-Sheva area in view of the higher ethnic diversity in this region, as compared to that in Israel as a whole. There were no differences in the clinicopathologic features of prostate carcinoma in the various population groups apart from those found between the East European and North African groups. The North African patients with prostate adenocarcinoma tended to be diagnosed and treated surgically at a younger age than those of East European origin. The reason for the difference is not clear. The older age at diagnosis may have prevented some of the East European patients from being eligible for radical surgery. A study of extended cohorts of these 2 groups that would include environmental factors, such as viral, nutritional, alcohol consumption, and smoking habits, as well as genetic factors, would seem to be warranted. The unexpected paucity of Bedouin subjects in our study may signify a low incidence of prostate adenocarcinoma. However, it may suggest their low compliance to medical prostate examination. Surprisingly, no immigrants of Ethiopian origin were diagnosed with prostate adenocarcinoma, although the Ethiopian population may be considered a priori to have features in common with the African-American population in the United States. It is noteworthy that the rate of autopsy examination in the Ethiopian as well as Bedouin population is very low at our center. This result would prevent more objective evaluation of the true incidence of prostate adenocarcinoma [18]. Our figures probably represent a gross underestimation of prostate adenocarcinoma among the Ethiopian and Bedouin groups. The reason for their lack of representation in our cohort may be the result of a cultural behavior pattern that prevents them from seeking medical consultation regarding their genitourinary problems. Education on medical subjects, including prostate cancer and screening programs among the Ethiopian and Bedouin communities, should be considered. Regarding the biologic markers studied, we found that the patients from East Europe had a higher expression of Bcl-2 in their prostate tumors. Bcl-2 is an apoptosis-inhibiting factor protein that may enhance the stability of tumor to the radiotherapy in different populations [19]. Further studies evaluating the response of the different groups to radiotherapy are warranted. Higher values of TP53 are expressed in malignant tumors showing more aggressive behavior. No significant change of expression of this marker in prostate cancer was seen in the different ethnic groups in our study. Prostate carcinoma that escapes antiandrogenic treatment shows a higher expression of neuroendocrine features, including chromogranin A [9,10]. No significant immunostaining differences of chromogranin A were detected in the different ethnic groups in our study.
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5. Conclusions We found ethnic differences in the clinical and biologic features of prostate adenocarcinoma in Southern Israel. There were more significant differences in the 2 largest Jewish population groups in South Israel. The patients of North African origin were diagnosed and treated at a younger age. A cultural difference in seeking help for genitourinary complaints may account for this finding. However, a genetic/familial difference is not excluded. No pathogenic clue regarding prostate adenocarcinoma was revealed in our study, but there were differences in the biologic characteristics of the tumor between the 2 largest population groups. It has been suggested that because these 2 groups originate from common ancestors [4], environmental factors such as cigarette smoking, viral infection, dietetic factors, or other chemical exposure may explain some of the differences.
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