The Prostate 75:917–922 (2015)
Latent Prostate Cancer in Japanese Men Who Die Unnatural Deaths: A Forensic Autopsy Study Masahito Kido,1 Masahito Hitosugi,2* Kanto Ishii,3 Shuichi Kamimura,4 and Kensuke Joh5 1
Department of Urology, Jikei University School of Medicine, Tokyo, Japan Department of Legal Medicine, Shiga University of Medical Science, Otsu, Japan 3 Department of Legal Medicine, Dokkyo Medical University, Shimotsuga, Japan 4 Department of Urology, Utsunomiya Nishigaoka Hospital, Utsunomiya, Japan 5 Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan 2
BACKGROUND. An accurate natural history of prostate cancer (PC) can be obtained from forensic autopsies of individuals who had performed their normal daily activities immediately before death and had not undergone long-term medical interventions. A retrospective analysis of such individuals was performed to understand the features of latent PC in Japan. METHODS. The findings of forensic autopsies performed at Dokkyo Medical University from August 2002 to July 2005 on men without severely destroyed or severely decomposed tissues were collected. Two cross sections, at the base and apex of the prostate, were examined histopathologically. Data collected included basic history, cause of death, location of PC, and Gleason score. RESULTS. Of 196 forensically autopsied males aged 0–90 years, 24 (12.7%) had latent PC. When analyzed by age group, PC was most prevalent among individuals in their eighties (33.3%). The prevalence of PC was similar in males who died of disease and of external causes. Most PCs were located at the base of the prostate, but were present on both the anterior and posterior sides. Nine of the 24 autopsied individuals also had other diseases, with three having cancers other than PC. CONCLUSIONS. This is the first report of the features of latent PC in Asian men who died of unnatural causes. Forensic autopsies can clarify the natural history of PC and may help fill knowledge gaps regarding latent PC. Prostate 75:917–922, 2015. # 2015 Wiley Periodicals, Inc. KEY WORDS:
prostate cancer; latent; unnatural death; forensic autopsy; Japanese
INTRODUCTION Prostate cancer (PC) is an indolent disease with a low probability of progressing to clinically lethal cancer. Although the lifetime risk of a diagnosis of PC among men in North America is about 17.0%, the risk of dying of PC is only 3.4% [1]. Therefore, overtreatment of low-risk PCs can introduce problems associated with the potential side effects of treatment, including sexual impotence and urinary incontinence, as well as the costs of treatment. Determination of the prevalence and characteristics of latent PC may provide understanding of its natural history. Historically, latent PC was mainly assessed during pathological autopsy [2–9]. However, most of these individuals had already been ß 2015 Wiley Periodicals, Inc.
diagnosed with diseases in a hospital. These patients had malignant or chronic diseases and had received medications including hormones and anticancer agents. Therefore, the findings of latent PC
Conflicts of interest: The authors report no conflicts of interest related to this study. Correspondence to: Masahito Hitosugi, MD, PhD, Department of Legal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192, Japan. E-mail: [email protected] Received 20 October 2014; Accepted 9 January 2015 DOI 10.1002/pros.22975 Published online 1 March 2015 in Wiley Online Library (wileyonlinelibrary.com).
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in these pathological autopsies may have been altered by these medical interventions. However, forensic autopsies are performed to determine causes of unnatural death, including sudden death from disease or external causes, such as accidents, suicide, and homicide. Because such individuals had performed their normal daily activities immediately before death and not undergone long-term medical interventions, the natural history of PC can be more accurately evaluated using forensic autopsy specimens. This study therefore evaluated the histopathological changes in prostate tissue specimens obtained from forensic autopsies. The incidence and characteristics of latent PC in Japan were determined.
approved by the Ethics Committee of Shiga University of Medical Science. At autopsy, the prostate gland was removed and cut into three parts vertical to the urethra. Two cross sections, one each at the base and apex of the prostate, were embedded in paraffin and stained with hematoxylin and eosin using standardized protocols. Prostate Examination PCs were identified and Gleason score (GS) assessed by a single experienced pathologist (K.J.) according to previously established morphologic criteria [10,11]. The location of each PC was mapped on a schema of the prostate.
MATERIALS AND METHODS Specimens Prostate specimens were collected from forensic autopsies performed at Dokkyo Medical University, located in Tochigi prefecture in the northern part of Kanto, Japan, from August 2002 to July 2005. The autopsy results of females and of bodies severely destroyed by trauma or severely decomposed were excluded. Of the 288 individuals autopsied during this time period, 196 were included in this analysis, with all bodies autopsied within 48 hr of death. Because forensic autopsies routinely include pathological examinations of the entire body, prostates of males are usually examined, both macroscopically and microscopically. Therefore, collection, processing, and examination of the prostate were not beyond the routine forensic autopsy protocol. This study was
Fig. 1.
Age distribution of all deceased individuals and those with PC.
The Prostate
Statistical Analysis The chi-squared test was used to compare the prevalence of PC in men who died of disease and those who die of external causes. Differences with a P-value of 49-years of age was 18.1%. Table I summarizes the medical history and GS among all individuals with PC according to their cause of death. The prevalence of PC was similar in men who died of disease and of external causes (10.3% vs 11.9%; P > 0.05). Nine of the 24 individuals with PC had other diseases, including three who had cancers other than PC.
Screening by measurement of serum concentrations of prostate-specific antigen is effective in reducing PC-related mortality [12]. However, PC screening can lead to overtreatment of patients with low biological risk, causing unnecessarily high morbidity and cost. Because a large proportion of PCs do not become life-threatening, overtreatment of latent PCs based on screening results must be avoided.
PC Locations PC locations are shown in Figure 2. Most PCs were located at the base of the prostate gland, on both the anterior and posterior sides.
Various methods have been utilized to assess the prevalence of latent PC throughout the world [2–9]. However, differences in methods and/or subject populations have precluded direct comparisons of these prevalence rates. Although most studies used samples obtained during pathological autopsy, many of these individuals had undergone medical interventions, were elderly at the time of death, or had cancers other than PC. This has introduced bias, limiting the utility of research using pathological autopsy specimens. To overcome the limitations of pathological autopsy, forensic autopsy specimens have been assessed for the prevalence of PC using similar methodology. Our study found that the prevalence of
TABLE I. Summary of Deceased Individuals With PC. Gleason Score, Age, and Medical History of Each Individual are Shown Relative to Cause of Death Cause of death Sudden natural death
External causes
Unknown
No.
Age
Gleason score
Past medical history
1 2 3 4 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 1 2 3
54 58 70 84 41 55 57 57 62 63 71 74 75 76 76 78 78 80 84 87 89 58 60 66
3þ3 2+2 4+4 4+4 5þ4 2þ2 3þ3 3þ4 4þ5 2þ1 2þ1 4þ5 5þ3 5þ5 3þ3 3þ2 5þ4 4þ5 4þ3 4þ5 2þ2 2þ3 4þ3 5þ5
Gastric cancer n. p. n. p. n. p. n. p. n. p. n. p. n. p. Colon cancer n. p. Lung cancer Chronic renal failure Diabetes mellitus, myocardial infarction n. p. n. p. Cerebral infarction, hypertension Alcoholism n. p. n. p. n. p. n. p. n. p. Hypertension, Parkinson disease n. p.
n.p., not particular. The Prostate
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Kido et al.
Fig. 2.
Distribution of PCs at the apex and base of prostate specimens.
PC was similar in men who died suddenly from disease and from external causes, indicating that the use of forensic autopsy specimens, including of individuals who died suddenly of disease and of external causes, can determine the prevalence of latent PC. Two previous studies have assessed the prevalence of latent PC in forensic specimens from Australia and Iran (Table II) [13,14]. Although tissue processing methods differed, the overall prevalence of PC in Australia and Japan was similar, 14.2% in Australia and 12.2% in Japan. However, the prevalence of latent PC in men aged >50-years differed substantially in Australia (25.7%), Japan (18.1%), and Iran (9.4%). Although the number of prostate tissue sections assayed was highest in Iran, the prevalence of PC was lowest. In contrast, the number of sections assayed was lowest in Australia, but the prevalence of PC was the highest. Although there were some differences in incidence and mortality rates, studies performed more than 25 years ago found that the geographic differences in the prevalence of PC were small [7,15,16]. However, time-related trends must be considered, along with changes in lifestyle. Although our study and two previous studies [13,14] using forensic materials were performed within a few years of each other, dietary differences among these regions
may have influenced the development of PC [17]. To our knowledge, this study is the first to evaluate latent PC using forensic autopsy specimens from an Asian population. Determination of the actual prevalence of PC in forensic autopsy specimens obtained in various geographic areas and comparisons of age groups, races, and geographic regions are necessary to confirm our findings. In the present study, PC was found in deceased persons aged 41-years. Because the autopsied individuals ranged in age from 0 to 90 years, we were able to detect PC at younger ages. Our findings were in accordance with those of a previous study, in which PC was found during forensic autopsy of individuals in their thirties [14]. Because some PCs may pass through a period of latency lasting up to 15 to 20 years, these results may be helpful in controlling PCs identified at younger ages. However, it remains unclear whether PCs that develop at younger ages are aggressive and high-risk. Clinically significant PC has been defined as tumors with a GS 7. PCs that do not meet this criterion are regarded as clinically insignificant and unlikely to adversely affect the health of the patient. Of the 24 latent PCs identified, 14 (58.3%) had a GS 7, a rate similar to that recently observed among
TABLE II. Summary of Reports, Including the Present Report, of Latent PCs Determined Using Forensic Autopsy Specimens
Reference
Country
Survey period
No. of victims
Victims’ age
No. of histological section
Prevalence of occult cancer
No. 13 No. 14 Present
Iran Australia Japan
2008–2009 2005–2006 2002–2005
140 133 196
>50 14–92 0–90
6 1 2
9.4% 14.3% 12.7%
No., number. The Prostate
Prostate Cancer in Forensic Autopsies pathological autopsies in Japan [2]. The prevalence of tumors with GS 7 was higher in Japanese than in Russian, European, and American men [3]. When the locations of latent PCs were mapped, most were found in the peripheral zone, similar to findings in Japanese, white Americans, and African Americans [18]. Furthermore, most of the PCs in the present study were located at the base of the prostate and were widely distributed throughout the anterior and posterior sides. These findings indicate the optimal biopsy sites for identification of clinically significant PCs. The most important limitation of this study was our making of two cross sections of each prostate specimen. As each prostate was divided into three equal sizes, whereas the size of the prostate depended on the body size of the victim, section intervals were not uniform. Section thickness during prostate processing may have influenced the prevalence of PC because thinner sections increase the rate of detection of small tumors. Another limitation was that the data from forensic autopsies were previously collected during routine forensic work. However, because the specimens were obtained from individuals who had died suddenly and included males of all ages, ranging from 0 to 90 years with a normal distribution, these results were likely reliable. Furthermore, the prevalence of PC among individuals in their forties was 5%, higher than in a recent study that evaluated pathological autopsy specimens of entire prostate glands sectioned at 4 mm intervals [2]. We found that the overall prevalence of PC in Japanese men aged >49-years was lower than in a previous study using Japanese pathological autopsy materials. However, comparisons are difficult because of the limitations of both studies. Finally, of the 24 deceased individuals with PC in our study, three had cancers other than PC and six had other diseases including lifestyle-related diseases. Because the potential risk factors for PC include diet, physical activity, and exposure to chemicals and carcinogens, patient medical history may have influenced the occurrence of PC [19]. Future studies assessing the prevalence of PC should compare subjects with and without considering their medical history. CONCLUSION Of 196 deceased males aged 0–90 years who were forensically autopsied from 2002 to 2005 in Japan, 24 (12.7%) had latent PC. The prevalence of PC was highest among individuals in their eighties (33.3%). Most PCs were located at the base of the prostate, but
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were widely distributed throughout the anterior and posterior sides. Forensic autopsies may help clarify the natural history of PC, especially of latent PC. ACKNOWLEDGMENT The authors gratefully acknowledge Junko Maeda and Yumie Tsunoda, the clinical technicians who provided the pathological specimens. REFERENCES 1. Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, Bray F. International variation in prostate cancer incidence and mortality rates. Eur Urol 2012;61(6):1079–1092. 2. Zlotta AR, Egawa S, Pushkar D, Govorov A, Kimura T, Kido M, Takahashi H, Kuk C, Kovylina M, Aldaoud N, Fleshner N, Finelli A, Klotz L, Sykes J, Lockwood G, Van der Kwast TH. Prevalence of prostate cancer on autopsy: Cross-sectional study on unscreened Caucasian and Asian Men. J Natl Cancer Inst 2013;105:1050–1058. 3. Stamatiou K, Alevizos A, Perimeni D, Sofras F, Agapitos E. Frequency of impalpable prostate adenocarcinoma and precancerous conditions in Greek male population: An autopsy study. Prostate Cancer Prostatic Dis 2006;9(1):45–49. 4. Soos G, Tsakiris I, Szanto J, Turzo C, Haas PG, Dezso B. The prevalence of prostate carcinoma and its precursor in Hungary: An autopsy study. Eur Urol 2005;48(5):739–744. 5. Sanchez-Chapado M, Olmedilla G, Cabeza M, Donat E, Ruiz A. Prevalence of prostate cancer and prostatic intraepithelial neoplasia in Caucasian Mediterranean males: An autopsy study. Prostate 2003;54(3):238–247. 6. Stemmermann GN, Nomura AM, Chyou PH, Yatani R. A prospective comparison of prostate cancer at autopsy and as a clinical event: The Hawaii Japanese experience. Cancer Epidemiol Biomarkers Prev 1992;1(3):189–193. 7. Yatani R, Shiraishi T, Nakakuki K, Kusano I, Takanari H, Hayashi T, Stemmermann GN. Trends in frequency of latent prostate carcinoma in Japan from 1965–1979 to 1982–1986. J Natl Cancer Inst 1988;80:683–687. 8. Bean MA, Yatani R, Liu PI, Fukazawa K, Ashley FW, Fujita S. Prostatic carcinoma at autopsy in Hiroshima and Nagasaki Japanese. Cancer 1973;32(2):498–506. 9. Akazaki K, Stemmermann GN. Comparative study of latent carcinoma of the prostate among Japanese in Japan and Hawaii. Natl Cancer Inst 1973;50:1137–1144. 10. Bostwick DG, Graham SD, Jr, Napalkov P, Abrahamsson PA, di Sant’agnese PA, Algaba F, Hoisaeter PA, Lee F, Littrup P, Mostofi FK, Abrahamsson PA, Denis L, Di Sant’agnese PA, Schroeder F, Algaba F, Murphy GP, Hoisaeter PA. Staging of early prostate cancer: A proposed tumor volume-based prognostic index. Urology 1993;41(5):403–411. 11. Bostwick DG, Amin MB, Dundore P, Marsh W, Schltz DS. Architectural patterns of high-grade prostatic intraepithelial neoplasia. Hum Pathol 1993;24(3):298–310. 12. Schr€ oder FH, Hugosson J, Roobol MJ, Tammela TL, Zappa M, Nelen V, Kwiatkowski M, Lujan M, M€ a€ att€ anen L, Lilja H, Denis LJ, Recker F, Paez A, Bangma CH, Carlsson S, Puliti D, Villers A, Rebillard X, Hakama M, Stenman UH, Kujala P, Taari K, Aus G, Huber A, van der Kwast TH, van Schaik RH, The Prostate
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de Koning HJ, Moss SM, Auvinen A. For the ERSPC Investigators. Screening and prostate cancer mortakity: Results of the European randomized study of screening for prostate cancer (ERSPC) at 13 years of follow up. Lancet. 2014;384(9959):2027–2035.
16. Breslow N, Chan CW, Dhom G, Drury RA, Franks LM, Gellei B, Lee YS, Lundberg S, Sparke B, Sternby NH, Tulinius H. Latent carcinoma of prostate at autopsy in seven areas. The International Agency for Research on Cancer, Lyons, France. Int J Cancer 1977;20(5):680–688.
13. Zale-Mirzaie A, Balvayeh P, Imamhadi MA, Lotfi M. The frequency of latent prostate carcinoma in autopsies of over 50 years old males, the Iranian experience. Med J Islam Republic Iran 2012;26(2):73–77.
17. Boyle P, Maisonneuve P, Napalkov P. Incidence of prostate cancer will double by the year 2030: The argument for. Eur Urol 1996;29(Suppl 2):3–9.
14. Orde MM, Whitaker NJ, Lawson JS. High prevalence of prostatic neoplasia in Australian men. Pathology 2009;42(5): 433–435.
18. Watanabe M, Nakatama T, Shiraishi T, Stemmermann GN, Yatani R. Comparative studies of prostate cancer in Japan versus the United States, A review. Urol Oncol 2000;5: 274–283.
15. Franks LM. Latent carcinoma. Annl Royal Coll Surg Eng 1954;15(4):236–249.
19. Mettlin C. Recent developments in the epidemiology of prostate cancer. Eur J Cancer 1997;33:340–347.
The Prostate
Latent Prostate Cancer in Japanese Men Who Die Unnatural Deaths: A Forensic Autopsy Study Masahito Kido,1 Masahito Hitosugi,2* Kanto Ishii,3 Shuichi Kamimura,4 and Kensuke Joh5 1
Department of Urology, Jikei University School of Medicine, Tokyo, Japan Department of Legal Medicine, Shiga University of Medical Science, Otsu, Japan 3 Department of Legal Medicine, Dokkyo Medical University, Shimotsuga, Japan 4 Department of Urology, Utsunomiya Nishigaoka Hospital, Utsunomiya, Japan 5 Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan 2
BACKGROUND. An accurate natural history of prostate cancer (PC) can be obtained from forensic autopsies of individuals who had performed their normal daily activities immediately before death and had not undergone long-term medical interventions. A retrospective analysis of such individuals was performed to understand the features of latent PC in Japan. METHODS. The findings of forensic autopsies performed at Dokkyo Medical University from August 2002 to July 2005 on men without severely destroyed or severely decomposed tissues were collected. Two cross sections, at the base and apex of the prostate, were examined histopathologically. Data collected included basic history, cause of death, location of PC, and Gleason score. RESULTS. Of 196 forensically autopsied males aged 0–90 years, 24 (12.7%) had latent PC. When analyzed by age group, PC was most prevalent among individuals in their eighties (33.3%). The prevalence of PC was similar in males who died of disease and of external causes. Most PCs were located at the base of the prostate, but were present on both the anterior and posterior sides. Nine of the 24 autopsied individuals also had other diseases, with three having cancers other than PC. CONCLUSIONS. This is the first report of the features of latent PC in Asian men who died of unnatural causes. Forensic autopsies can clarify the natural history of PC and may help fill knowledge gaps regarding latent PC. Prostate 75:917–922, 2015. # 2015 Wiley Periodicals, Inc. KEY WORDS:
prostate cancer; latent; unnatural death; forensic autopsy; Japanese
INTRODUCTION Prostate cancer (PC) is an indolent disease with a low probability of progressing to clinically lethal cancer. Although the lifetime risk of a diagnosis of PC among men in North America is about 17.0%, the risk of dying of PC is only 3.4% [1]. Therefore, overtreatment of low-risk PCs can introduce problems associated with the potential side effects of treatment, including sexual impotence and urinary incontinence, as well as the costs of treatment. Determination of the prevalence and characteristics of latent PC may provide understanding of its natural history. Historically, latent PC was mainly assessed during pathological autopsy [2–9]. However, most of these individuals had already been ß 2015 Wiley Periodicals, Inc.
diagnosed with diseases in a hospital. These patients had malignant or chronic diseases and had received medications including hormones and anticancer agents. Therefore, the findings of latent PC
Conflicts of interest: The authors report no conflicts of interest related to this study. Correspondence to: Masahito Hitosugi, MD, PhD, Department of Legal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192, Japan. E-mail: [email protected] Received 20 October 2014; Accepted 9 January 2015 DOI 10.1002/pros.22975 Published online 1 March 2015 in Wiley Online Library (wileyonlinelibrary.com).
918
Kido et al.
in these pathological autopsies may have been altered by these medical interventions. However, forensic autopsies are performed to determine causes of unnatural death, including sudden death from disease or external causes, such as accidents, suicide, and homicide. Because such individuals had performed their normal daily activities immediately before death and not undergone long-term medical interventions, the natural history of PC can be more accurately evaluated using forensic autopsy specimens. This study therefore evaluated the histopathological changes in prostate tissue specimens obtained from forensic autopsies. The incidence and characteristics of latent PC in Japan were determined.
approved by the Ethics Committee of Shiga University of Medical Science. At autopsy, the prostate gland was removed and cut into three parts vertical to the urethra. Two cross sections, one each at the base and apex of the prostate, were embedded in paraffin and stained with hematoxylin and eosin using standardized protocols. Prostate Examination PCs were identified and Gleason score (GS) assessed by a single experienced pathologist (K.J.) according to previously established morphologic criteria [10,11]. The location of each PC was mapped on a schema of the prostate.
MATERIALS AND METHODS Specimens Prostate specimens were collected from forensic autopsies performed at Dokkyo Medical University, located in Tochigi prefecture in the northern part of Kanto, Japan, from August 2002 to July 2005. The autopsy results of females and of bodies severely destroyed by trauma or severely decomposed were excluded. Of the 288 individuals autopsied during this time period, 196 were included in this analysis, with all bodies autopsied within 48 hr of death. Because forensic autopsies routinely include pathological examinations of the entire body, prostates of males are usually examined, both macroscopically and microscopically. Therefore, collection, processing, and examination of the prostate were not beyond the routine forensic autopsy protocol. This study was
Fig. 1.
Age distribution of all deceased individuals and those with PC.
The Prostate
Statistical Analysis The chi-squared test was used to compare the prevalence of PC in men who died of disease and those who die of external causes. Differences with a P-value of 49-years of age was 18.1%. Table I summarizes the medical history and GS among all individuals with PC according to their cause of death. The prevalence of PC was similar in men who died of disease and of external causes (10.3% vs 11.9%; P > 0.05). Nine of the 24 individuals with PC had other diseases, including three who had cancers other than PC.
Screening by measurement of serum concentrations of prostate-specific antigen is effective in reducing PC-related mortality [12]. However, PC screening can lead to overtreatment of patients with low biological risk, causing unnecessarily high morbidity and cost. Because a large proportion of PCs do not become life-threatening, overtreatment of latent PCs based on screening results must be avoided.
PC Locations PC locations are shown in Figure 2. Most PCs were located at the base of the prostate gland, on both the anterior and posterior sides.
Various methods have been utilized to assess the prevalence of latent PC throughout the world [2–9]. However, differences in methods and/or subject populations have precluded direct comparisons of these prevalence rates. Although most studies used samples obtained during pathological autopsy, many of these individuals had undergone medical interventions, were elderly at the time of death, or had cancers other than PC. This has introduced bias, limiting the utility of research using pathological autopsy specimens. To overcome the limitations of pathological autopsy, forensic autopsy specimens have been assessed for the prevalence of PC using similar methodology. Our study found that the prevalence of
TABLE I. Summary of Deceased Individuals With PC. Gleason Score, Age, and Medical History of Each Individual are Shown Relative to Cause of Death Cause of death Sudden natural death
External causes
Unknown
No.
Age
Gleason score
Past medical history
1 2 3 4 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 1 2 3
54 58 70 84 41 55 57 57 62 63 71 74 75 76 76 78 78 80 84 87 89 58 60 66
3þ3 2+2 4+4 4+4 5þ4 2þ2 3þ3 3þ4 4þ5 2þ1 2þ1 4þ5 5þ3 5þ5 3þ3 3þ2 5þ4 4þ5 4þ3 4þ5 2þ2 2þ3 4þ3 5þ5
Gastric cancer n. p. n. p. n. p. n. p. n. p. n. p. n. p. Colon cancer n. p. Lung cancer Chronic renal failure Diabetes mellitus, myocardial infarction n. p. n. p. Cerebral infarction, hypertension Alcoholism n. p. n. p. n. p. n. p. n. p. Hypertension, Parkinson disease n. p.
n.p., not particular. The Prostate
920
Kido et al.
Fig. 2.
Distribution of PCs at the apex and base of prostate specimens.
PC was similar in men who died suddenly from disease and from external causes, indicating that the use of forensic autopsy specimens, including of individuals who died suddenly of disease and of external causes, can determine the prevalence of latent PC. Two previous studies have assessed the prevalence of latent PC in forensic specimens from Australia and Iran (Table II) [13,14]. Although tissue processing methods differed, the overall prevalence of PC in Australia and Japan was similar, 14.2% in Australia and 12.2% in Japan. However, the prevalence of latent PC in men aged >50-years differed substantially in Australia (25.7%), Japan (18.1%), and Iran (9.4%). Although the number of prostate tissue sections assayed was highest in Iran, the prevalence of PC was lowest. In contrast, the number of sections assayed was lowest in Australia, but the prevalence of PC was the highest. Although there were some differences in incidence and mortality rates, studies performed more than 25 years ago found that the geographic differences in the prevalence of PC were small [7,15,16]. However, time-related trends must be considered, along with changes in lifestyle. Although our study and two previous studies [13,14] using forensic materials were performed within a few years of each other, dietary differences among these regions
may have influenced the development of PC [17]. To our knowledge, this study is the first to evaluate latent PC using forensic autopsy specimens from an Asian population. Determination of the actual prevalence of PC in forensic autopsy specimens obtained in various geographic areas and comparisons of age groups, races, and geographic regions are necessary to confirm our findings. In the present study, PC was found in deceased persons aged 41-years. Because the autopsied individuals ranged in age from 0 to 90 years, we were able to detect PC at younger ages. Our findings were in accordance with those of a previous study, in which PC was found during forensic autopsy of individuals in their thirties [14]. Because some PCs may pass through a period of latency lasting up to 15 to 20 years, these results may be helpful in controlling PCs identified at younger ages. However, it remains unclear whether PCs that develop at younger ages are aggressive and high-risk. Clinically significant PC has been defined as tumors with a GS 7. PCs that do not meet this criterion are regarded as clinically insignificant and unlikely to adversely affect the health of the patient. Of the 24 latent PCs identified, 14 (58.3%) had a GS 7, a rate similar to that recently observed among
TABLE II. Summary of Reports, Including the Present Report, of Latent PCs Determined Using Forensic Autopsy Specimens
Reference
Country
Survey period
No. of victims
Victims’ age
No. of histological section
Prevalence of occult cancer
No. 13 No. 14 Present
Iran Australia Japan
2008–2009 2005–2006 2002–2005
140 133 196
>50 14–92 0–90
6 1 2
9.4% 14.3% 12.7%
No., number. The Prostate
Prostate Cancer in Forensic Autopsies pathological autopsies in Japan [2]. The prevalence of tumors with GS 7 was higher in Japanese than in Russian, European, and American men [3]. When the locations of latent PCs were mapped, most were found in the peripheral zone, similar to findings in Japanese, white Americans, and African Americans [18]. Furthermore, most of the PCs in the present study were located at the base of the prostate and were widely distributed throughout the anterior and posterior sides. These findings indicate the optimal biopsy sites for identification of clinically significant PCs. The most important limitation of this study was our making of two cross sections of each prostate specimen. As each prostate was divided into three equal sizes, whereas the size of the prostate depended on the body size of the victim, section intervals were not uniform. Section thickness during prostate processing may have influenced the prevalence of PC because thinner sections increase the rate of detection of small tumors. Another limitation was that the data from forensic autopsies were previously collected during routine forensic work. However, because the specimens were obtained from individuals who had died suddenly and included males of all ages, ranging from 0 to 90 years with a normal distribution, these results were likely reliable. Furthermore, the prevalence of PC among individuals in their forties was 5%, higher than in a recent study that evaluated pathological autopsy specimens of entire prostate glands sectioned at 4 mm intervals [2]. We found that the overall prevalence of PC in Japanese men aged >49-years was lower than in a previous study using Japanese pathological autopsy materials. However, comparisons are difficult because of the limitations of both studies. Finally, of the 24 deceased individuals with PC in our study, three had cancers other than PC and six had other diseases including lifestyle-related diseases. Because the potential risk factors for PC include diet, physical activity, and exposure to chemicals and carcinogens, patient medical history may have influenced the occurrence of PC [19]. Future studies assessing the prevalence of PC should compare subjects with and without considering their medical history. CONCLUSION Of 196 deceased males aged 0–90 years who were forensically autopsied from 2002 to 2005 in Japan, 24 (12.7%) had latent PC. The prevalence of PC was highest among individuals in their eighties (33.3%). Most PCs were located at the base of the prostate, but
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were widely distributed throughout the anterior and posterior sides. Forensic autopsies may help clarify the natural history of PC, especially of latent PC. ACKNOWLEDGMENT The authors gratefully acknowledge Junko Maeda and Yumie Tsunoda, the clinical technicians who provided the pathological specimens. REFERENCES 1. Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, Bray F. International variation in prostate cancer incidence and mortality rates. Eur Urol 2012;61(6):1079–1092. 2. Zlotta AR, Egawa S, Pushkar D, Govorov A, Kimura T, Kido M, Takahashi H, Kuk C, Kovylina M, Aldaoud N, Fleshner N, Finelli A, Klotz L, Sykes J, Lockwood G, Van der Kwast TH. Prevalence of prostate cancer on autopsy: Cross-sectional study on unscreened Caucasian and Asian Men. J Natl Cancer Inst 2013;105:1050–1058. 3. Stamatiou K, Alevizos A, Perimeni D, Sofras F, Agapitos E. Frequency of impalpable prostate adenocarcinoma and precancerous conditions in Greek male population: An autopsy study. Prostate Cancer Prostatic Dis 2006;9(1):45–49. 4. Soos G, Tsakiris I, Szanto J, Turzo C, Haas PG, Dezso B. The prevalence of prostate carcinoma and its precursor in Hungary: An autopsy study. Eur Urol 2005;48(5):739–744. 5. Sanchez-Chapado M, Olmedilla G, Cabeza M, Donat E, Ruiz A. Prevalence of prostate cancer and prostatic intraepithelial neoplasia in Caucasian Mediterranean males: An autopsy study. Prostate 2003;54(3):238–247. 6. Stemmermann GN, Nomura AM, Chyou PH, Yatani R. A prospective comparison of prostate cancer at autopsy and as a clinical event: The Hawaii Japanese experience. Cancer Epidemiol Biomarkers Prev 1992;1(3):189–193. 7. Yatani R, Shiraishi T, Nakakuki K, Kusano I, Takanari H, Hayashi T, Stemmermann GN. Trends in frequency of latent prostate carcinoma in Japan from 1965–1979 to 1982–1986. J Natl Cancer Inst 1988;80:683–687. 8. Bean MA, Yatani R, Liu PI, Fukazawa K, Ashley FW, Fujita S. Prostatic carcinoma at autopsy in Hiroshima and Nagasaki Japanese. Cancer 1973;32(2):498–506. 9. Akazaki K, Stemmermann GN. Comparative study of latent carcinoma of the prostate among Japanese in Japan and Hawaii. Natl Cancer Inst 1973;50:1137–1144. 10. Bostwick DG, Graham SD, Jr, Napalkov P, Abrahamsson PA, di Sant’agnese PA, Algaba F, Hoisaeter PA, Lee F, Littrup P, Mostofi FK, Abrahamsson PA, Denis L, Di Sant’agnese PA, Schroeder F, Algaba F, Murphy GP, Hoisaeter PA. Staging of early prostate cancer: A proposed tumor volume-based prognostic index. Urology 1993;41(5):403–411. 11. Bostwick DG, Amin MB, Dundore P, Marsh W, Schltz DS. Architectural patterns of high-grade prostatic intraepithelial neoplasia. Hum Pathol 1993;24(3):298–310. 12. Schr€ oder FH, Hugosson J, Roobol MJ, Tammela TL, Zappa M, Nelen V, Kwiatkowski M, Lujan M, M€ a€ att€ anen L, Lilja H, Denis LJ, Recker F, Paez A, Bangma CH, Carlsson S, Puliti D, Villers A, Rebillard X, Hakama M, Stenman UH, Kujala P, Taari K, Aus G, Huber A, van der Kwast TH, van Schaik RH, The Prostate
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The Prostate
