- Email: [email protected]
147 DNA methylation profile of 28 candidate marker loci in malignant mesothelioma
S36 144
Saturday, October 21, 2006 / Poster discussion session: The high-risk individual III Prognostic factors and survival of malignant mesothelioma in Korea
H.R. Kim 1 , Y.K. Chung 1 , S.H. Jung 2 , Y. Chung 2 . 1 The Catholic University of Korea, Seoul, Korea; 2 Dept. of Pathology Yonsei University Wonju College of Medicine, Korea Background: Malignant mesothelioma surveillance has been accomplished since 2001 in Korea. It consists of active and passive systems. In passive system, pathologists who work for general hospitals are core participants. The cancer registry system and the national mortality statistics were used in the active system. The aim of this study is to evaluate the survival rate and the prognostic factors related to survival duration of malignant mesothelioma by using the Korea’s malignant mesothelioma surveillance data and the national mortality statistics. Methods: Individual data for mesothelioma were retrieved from the Korea’s Malignant Mesothelioma Surveillance System during the period 2001-2005. The survival analysis was performed with the Kaplan-Meier method, based on the newly reported cases diagnosed during the period 1993-2002. 1-year fatality rate was calculated to investigate diagnosis date and death date. According to the 1-year fatality, age, gender, living area, occurring lesion and histological type were compared by chi-square test. Results: The result shows that the survival of malignant mesothelioma was very poor (5-year survival and median survival time: 27.5% and 12 months, and 1-year survival: 47.6%). Cases who live in big cities have much higher 1year fatality rate than others. We also found that people who are over 50 years old, and have pleural lesion are related to poor prognosis (by chi-square test). Multivariate analysis also revealed similar results (living in a big city has a strong relation with poor prognosis). Conclusions: Five-year and one-year survival of patients with malignant mesothelioma was very poor and living in a big city is another poor prognostic factor. In the future, more various factors related to prognosis of malignant mesothelioma (e.g. occupational and environmental exposure) should be investigated.
145
Clinico-pathologic analysis of malignant mesothelioma in Korea
S. Jung 1 , Y. Chong 1 , H. Kim 2 , Y. Chung 2 , S. Koh 1 , S. Yong 1 , B. Choi 3 , Y. Ahn 3 . 1 Yonsei University Wonju College of Medicine; 2 The Catholic University of Korea, Seoul, Korea; 3 Korea Occupational Safety and Health Research Institute, Korea Background: This study estimated the magnitude of malignant mesothelioma in Korea and its clinicopathologic features. We collected 137 cases through the Korea Malignant Mesothelioma Surveillance System (KMMS) from 2001 to 2005. Methods: We established a surveillance system for malignant mesothelioma in 2001. Using the clinical information, epidemiological survey and pathological evaluations which have been collected from 23 University Hospitals by the members of Korean Pulmonary Pathologist Society, the patients’ age, sex, occupation history, tumor sites, specimen type with diagnostic method, histopathologic subtype and immunohistochemical results of the 137 cases were analyzed. Results: The patients were 85 men (62%) and 52 women (38%). The average age of the patients was 57 years. Among 86 cases with available occupational history, 24 (28%) were related with asbestos exposure occupation including construction industry, asbestos textile manufacturing industries, and asbestos painting. The distribution of sites was pleura (77%), peritoneum (19%), and pericardium (4%). Thirty-seven patients received a radical operation including extrapleural pleuropneumonectomy and others were diagnosed by the pathologic examination of biopsy, excision or cytologic specimen. The pathologic subtypes were epithelioid (70%), biphasic (14%), sarcomatous (8%), desmoplastic (3%), and variants (5%) in order. Based on the results of the immunohistochemical stains, we found the calretinin is the most sensitive marker (86.9%) for the diagnosis of malignant mesothelioma. Conclusions: The epithelioid subtype was most common in diffuse pleural malignant mesothelioma of Korea, however, the number of malignant mesothelioma patients and the relation rate with occupational asbestos exposure were relatively low. The surveillance system of malignant mesothelioma in Korea supplemented by an active surveillance system using death certificate data and cancer registry data could be helpful to understand the more exact status of malignant mesothelioma of Korea.
146
Asbestos problems in India: A revisit
V. Subramanian. Jawaharlal Nehru University, New Delhi, India Asbestos is no longer an issue confined only to health issues in mining and milling. It is now a generalized issue of concern in occupational health. The recent controversy about the French ship led to intense debate on trans-boundary
movement of all hazardous substances including asbestos. A Norwegian ship also had to go away from India. The safe disposal of asbestos in old ships, however small in amount, has not been found and this is urgent need for research. Ship breaking in India has come down to 75 from a high of 350. The side effect of this drop in number is unemployment of the migrant labor population and this exposes the traditional conflict between environment and development. Good health is a must but this population has to live and survive; if there are no jobs at all, occupational health issues such as asbestos becomes only an academic issue. There are conflicting studies on asbestos exposure levels in work places in India. In a most recent report, Ansari et al.,(2006, in press) claim that levels of asbestos in air around milling and manufacturing areas near a factory in Punjab are below the standards (0.04 fibres/cc as against the BIS values of 0.5 fibres/cc). The pollution control authority in India wants a limit of 0.1 fibre/cc. The threshold values in mining and milling areas in India is 2 fibres/cc. Hence, the fundamental issue of asbestos problem in India is lack of a unified approach in addressing health issues while ban the asbestos groups are rather united but without looking into economically viable alternative for users and employment for the affected labor population. Marginal poor population is thus at odds with high decibel environmental populism.
Saturday, October 21, 2006
10:30–11:10
POSTER DISCUSSION SESSION
The high-risk individual III 147
DNA methylation profile of 28 candidate marker loci in malignant mesothelioma
J.A. Tsou 1 , J.S. Galler 1 , A. Wali 2 , H.I. Pass 3 , K.D. Siegmund 1 , W. Ye 1 , S. Groshen 1 , D. Weisenberger 1 , M. Campan 1 , P.W. Laird 1 , S. Turla 1 , M.N. Koss 1 , I.A. Laird-Offringa 1 . 1 University of Southern California, Los Angeles, USA; 2 Wayne State University, Detroit, USA; 3 New York Univeristy School of Medicine, New York, USA Background: Patients with malignant mesothelioma (MM), an aggressive cancer strongly associated with asbestos exposure, usually present with clinical symptoms at an advanced stage of the disease, which strongly reduces the likelihood of curative treatment. DNA methylation changes in the blood, pleural fluid or other bodily fluids of MM patients could provide a powerful non-invasive way to diagnose MM. Methods: Using the highly sensitive and quantitative PCR method, MethyLight, we examined the methylation status of 28 loci in MM tumors. To exclude candidate MM markers that might be positive in a biopsy due to contaminating lung tissue, we also examined the methylation of these markers in lung samples (methylation is frequently observed in non-cancerous lung due to environmental exposure and/or aging). Results: The loci MT1A, LZTS1, CDKN2AEX2, MT2A, and RASSF1 showed frequent and elevated methylation in MM, however, these loci were also frequently methylated in non-tumor lung. Statistically significant differences in methylation between MM samples and non-tumor lung samples were found for APC (p<0.0001), CDKN2B (p<0.0001), ATM (p=0.0001), ESR1 (p=0.0002), SYK (p=0.0003), and SLC6A20 (p=0.0022) (Mann-Whitney U test taking into account threshold for multiple comparisons). Examination of correlations between methylation levels and clinical parameters hints at associations of methylation status with gender, histology, asbestos exposure, lymph node involvement, and survival. Conclusions: Our results provide evidence for frequent methylation of genes in MM, and support the further development of DNA methylation markers as diagnostic, prognostic, and early detection tools for MM.
148
Asbestos exposure and genetic susceptibility to malignant pleural mesothelioma
S. Karageorgi 1 , B.C. Christensen 1 , M.D. McClean 2 , C.R. Roelofs 3 , D.J. Sugarbaker 4 , S. Byler 1 , K.T. Kelsey 1 , H.H. Nelson 1 . 1 Harvard School of Public Health, Boston, USA; 2 Boston University School of Public Health, Boston, USA; 3 University of Massachusetts, Lowell, USA; 4 Harvard Medical School and Brigham and Women’s Hospital, Boston, USA Background: Malignant pleural mesothelioma (MPM) is a rare disease that is known to be associated with exposure to asbestos. Familial patterning of cases has indicated that there is an inherited susceptibility to this disease and several small studies have previously suggested that several candidate gene variants modify the disease risk associated with asbestos exposure. We investigated whether polymorphisms in the DNA repair gene XRCC1, or the detoxification
Saturday, October 21, 2006 / Poster discussion session: The high-risk individual III Prognostic factors and survival of malignant mesothelioma in Korea
H.R. Kim 1 , Y.K. Chung 1 , S.H. Jung 2 , Y. Chung 2 . 1 The Catholic University of Korea, Seoul, Korea; 2 Dept. of Pathology Yonsei University Wonju College of Medicine, Korea Background: Malignant mesothelioma surveillance has been accomplished since 2001 in Korea. It consists of active and passive systems. In passive system, pathologists who work for general hospitals are core participants. The cancer registry system and the national mortality statistics were used in the active system. The aim of this study is to evaluate the survival rate and the prognostic factors related to survival duration of malignant mesothelioma by using the Korea’s malignant mesothelioma surveillance data and the national mortality statistics. Methods: Individual data for mesothelioma were retrieved from the Korea’s Malignant Mesothelioma Surveillance System during the period 2001-2005. The survival analysis was performed with the Kaplan-Meier method, based on the newly reported cases diagnosed during the period 1993-2002. 1-year fatality rate was calculated to investigate diagnosis date and death date. According to the 1-year fatality, age, gender, living area, occurring lesion and histological type were compared by chi-square test. Results: The result shows that the survival of malignant mesothelioma was very poor (5-year survival and median survival time: 27.5% and 12 months, and 1-year survival: 47.6%). Cases who live in big cities have much higher 1year fatality rate than others. We also found that people who are over 50 years old, and have pleural lesion are related to poor prognosis (by chi-square test). Multivariate analysis also revealed similar results (living in a big city has a strong relation with poor prognosis). Conclusions: Five-year and one-year survival of patients with malignant mesothelioma was very poor and living in a big city is another poor prognostic factor. In the future, more various factors related to prognosis of malignant mesothelioma (e.g. occupational and environmental exposure) should be investigated.
145
Clinico-pathologic analysis of malignant mesothelioma in Korea
S. Jung 1 , Y. Chong 1 , H. Kim 2 , Y. Chung 2 , S. Koh 1 , S. Yong 1 , B. Choi 3 , Y. Ahn 3 . 1 Yonsei University Wonju College of Medicine; 2 The Catholic University of Korea, Seoul, Korea; 3 Korea Occupational Safety and Health Research Institute, Korea Background: This study estimated the magnitude of malignant mesothelioma in Korea and its clinicopathologic features. We collected 137 cases through the Korea Malignant Mesothelioma Surveillance System (KMMS) from 2001 to 2005. Methods: We established a surveillance system for malignant mesothelioma in 2001. Using the clinical information, epidemiological survey and pathological evaluations which have been collected from 23 University Hospitals by the members of Korean Pulmonary Pathologist Society, the patients’ age, sex, occupation history, tumor sites, specimen type with diagnostic method, histopathologic subtype and immunohistochemical results of the 137 cases were analyzed. Results: The patients were 85 men (62%) and 52 women (38%). The average age of the patients was 57 years. Among 86 cases with available occupational history, 24 (28%) were related with asbestos exposure occupation including construction industry, asbestos textile manufacturing industries, and asbestos painting. The distribution of sites was pleura (77%), peritoneum (19%), and pericardium (4%). Thirty-seven patients received a radical operation including extrapleural pleuropneumonectomy and others were diagnosed by the pathologic examination of biopsy, excision or cytologic specimen. The pathologic subtypes were epithelioid (70%), biphasic (14%), sarcomatous (8%), desmoplastic (3%), and variants (5%) in order. Based on the results of the immunohistochemical stains, we found the calretinin is the most sensitive marker (86.9%) for the diagnosis of malignant mesothelioma. Conclusions: The epithelioid subtype was most common in diffuse pleural malignant mesothelioma of Korea, however, the number of malignant mesothelioma patients and the relation rate with occupational asbestos exposure were relatively low. The surveillance system of malignant mesothelioma in Korea supplemented by an active surveillance system using death certificate data and cancer registry data could be helpful to understand the more exact status of malignant mesothelioma of Korea.
146
Asbestos problems in India: A revisit
V. Subramanian. Jawaharlal Nehru University, New Delhi, India Asbestos is no longer an issue confined only to health issues in mining and milling. It is now a generalized issue of concern in occupational health. The recent controversy about the French ship led to intense debate on trans-boundary
movement of all hazardous substances including asbestos. A Norwegian ship also had to go away from India. The safe disposal of asbestos in old ships, however small in amount, has not been found and this is urgent need for research. Ship breaking in India has come down to 75 from a high of 350. The side effect of this drop in number is unemployment of the migrant labor population and this exposes the traditional conflict between environment and development. Good health is a must but this population has to live and survive; if there are no jobs at all, occupational health issues such as asbestos becomes only an academic issue. There are conflicting studies on asbestos exposure levels in work places in India. In a most recent report, Ansari et al.,(2006, in press) claim that levels of asbestos in air around milling and manufacturing areas near a factory in Punjab are below the standards (0.04 fibres/cc as against the BIS values of 0.5 fibres/cc). The pollution control authority in India wants a limit of 0.1 fibre/cc. The threshold values in mining and milling areas in India is 2 fibres/cc. Hence, the fundamental issue of asbestos problem in India is lack of a unified approach in addressing health issues while ban the asbestos groups are rather united but without looking into economically viable alternative for users and employment for the affected labor population. Marginal poor population is thus at odds with high decibel environmental populism.
Saturday, October 21, 2006
10:30–11:10
POSTER DISCUSSION SESSION
The high-risk individual III 147
DNA methylation profile of 28 candidate marker loci in malignant mesothelioma
J.A. Tsou 1 , J.S. Galler 1 , A. Wali 2 , H.I. Pass 3 , K.D. Siegmund 1 , W. Ye 1 , S. Groshen 1 , D. Weisenberger 1 , M. Campan 1 , P.W. Laird 1 , S. Turla 1 , M.N. Koss 1 , I.A. Laird-Offringa 1 . 1 University of Southern California, Los Angeles, USA; 2 Wayne State University, Detroit, USA; 3 New York Univeristy School of Medicine, New York, USA Background: Patients with malignant mesothelioma (MM), an aggressive cancer strongly associated with asbestos exposure, usually present with clinical symptoms at an advanced stage of the disease, which strongly reduces the likelihood of curative treatment. DNA methylation changes in the blood, pleural fluid or other bodily fluids of MM patients could provide a powerful non-invasive way to diagnose MM. Methods: Using the highly sensitive and quantitative PCR method, MethyLight, we examined the methylation status of 28 loci in MM tumors. To exclude candidate MM markers that might be positive in a biopsy due to contaminating lung tissue, we also examined the methylation of these markers in lung samples (methylation is frequently observed in non-cancerous lung due to environmental exposure and/or aging). Results: The loci MT1A, LZTS1, CDKN2AEX2, MT2A, and RASSF1 showed frequent and elevated methylation in MM, however, these loci were also frequently methylated in non-tumor lung. Statistically significant differences in methylation between MM samples and non-tumor lung samples were found for APC (p<0.0001), CDKN2B (p<0.0001), ATM (p=0.0001), ESR1 (p=0.0002), SYK (p=0.0003), and SLC6A20 (p=0.0022) (Mann-Whitney U test taking into account threshold for multiple comparisons). Examination of correlations between methylation levels and clinical parameters hints at associations of methylation status with gender, histology, asbestos exposure, lymph node involvement, and survival. Conclusions: Our results provide evidence for frequent methylation of genes in MM, and support the further development of DNA methylation markers as diagnostic, prognostic, and early detection tools for MM.
148
Asbestos exposure and genetic susceptibility to malignant pleural mesothelioma
S. Karageorgi 1 , B.C. Christensen 1 , M.D. McClean 2 , C.R. Roelofs 3 , D.J. Sugarbaker 4 , S. Byler 1 , K.T. Kelsey 1 , H.H. Nelson 1 . 1 Harvard School of Public Health, Boston, USA; 2 Boston University School of Public Health, Boston, USA; 3 University of Massachusetts, Lowell, USA; 4 Harvard Medical School and Brigham and Women’s Hospital, Boston, USA Background: Malignant pleural mesothelioma (MPM) is a rare disease that is known to be associated with exposure to asbestos. Familial patterning of cases has indicated that there is an inherited susceptibility to this disease and several small studies have previously suggested that several candidate gene variants modify the disease risk associated with asbestos exposure. We investigated whether polymorphisms in the DNA repair gene XRCC1, or the detoxification