Prevalence of p16 Methylation and Prognostic Factors in Plasma Cell Myeloma at a Single Institution in Korea
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: The primary purpose of this study was to investigate the prevalence and characteristics of p16 methylation and determine the prognostic implications of the clinical data, hematologic data, and p16 methylation changes in plasma cell myeloma (PCM). Methods: We reviewed clinical characteristics and results of laboratory tests and investigated the response to combination chemotherapy and survival time. DNA methylation of the p16 gene was tested by methylation-specific PCR. Clinical significance was evaluated. Results: A total of 103 patients were enrolled in this study. The median patient age was 59.0 yr at diagnosis and the male to female ratio was 1.15:1. According to the International Staging System (ISS), patients were diagnosed as stage: I (N=17, 16.5%), II (N=41, 39.8%), III (N=39, 37.9%), or not classified (N=6). Forty-five (43.7%) patients and 36 (35.0%) patients showed abnormal karyotype and complex karyotype, respectively, on the chromosome study. The p16 methylation was observed in 39 (37.9%) of 103 patients, but there was no significant association between p16 methylation status and other clinical or laboratory factors and survival outcome. Male gender, albumin, and complex karyotype were independent prognostic factors for overall survival according to multivariate analysis (P <0.05). Conclusions: The male gender, low serum albumin level, and complex karyotype were independent poor prognostic factors for PCM. p16 methylation was relatively common in PCM,but did not influence the survival outcome.
Abstract
Background: The primary purpose of this study was to investigate the prevalence and characteristics of p16 methylation and determine the prognostic implications of the clinical data, hematologic data, and p16 methylation changes in plasma cell myeloma (PCM). Methods: We reviewed clinical characteristics and results of laboratory tests and investigated the response to combination chemotherapy and survival time. DNA methylation of the p16 gene was tested by methylation-specific PCR. Clinical significance was evaluated. Results: A total of 103 patients were enrolled in this study. The median patient age was 59.0 yr at diagnosis and the male to female ratio was 1.15:1. According to the International Staging System (ISS), patients were diagnosed as stage: I (N=17, 16.5%), II (N=41, 39.8%), III (N=39, 37.9%), or not classified (N=6). Forty-five (43.7%) patients and 36 (35.0%) patients showed abnormal karyotype and complex karyotype, respectively, on the chromosome study. The p16 methylation was observed in 39 (37.9%) of 103 patients, but there was no significant association between p16 methylation status and other clinical or laboratory factors and survival outcome. Male gender, albumin, and complex karyotype were independent prognostic factors for overall survival according to multivariate analysis (P <0.05). Conclusions: The male gender, low serum albumin level, and complex karyotype were independent poor prognostic factors for PCM. p16 methylation was relatively common in PCM,but did not influence the survival outcome.
참고문헌 (27)
- "SEER Cancer Statistics Review" (1975)[URL]
- McKenna RW, "Plasma cell neoplasm, In WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed", pp.200~213 (2008), IARC
- Brenner H, "Expected long-term survival of patients diagnosed with multiple myeloma in 2006-2010", Haematologica, 94, pp.270~275 (2009)
- Jemal A, "Cancer statistics, 2008", CA Cancer J Clin, 58, pp.71~96 (2008)
- Avet-Loiseau H, "Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome", Blood, 109, pp.3489~3495 (2007)
- Bladé J, "Prognostic factors for multiple myeloma in the era of novel agents", Ann Oncol, 19(S7), pp.7117~7120 (2008)
- Smadja NV, "Hypodiploidy is a major prognostic factor in multiple myeloma", Blood, 98, pp.2229~2238 (2001)
- Gonzalez-Paz N, "Tumor suppressor p16 methylation in multiple myeloma: biological and clinical implications", Blood, 109, pp.1228~1232 (2007)
- Goto T, "Aberrant methylation of the p16 gene is frequently detected in advanced colorectal cancer", Anticancer Res, 29, pp.275~277 (2009)
- Ohashi H, "Relationship between methylation of the p15 gene and ectopic expression of the EVI-1 gene in myelodysplastic syndromes (MDS)", Leukemia, 15, pp.990~991 (2001)
- Guillerm G, "p16INK4a and p15INK4b gene methylations in plasma cells from monoclonal gammopathy of undetermined significance", Blood, 98, pp.244~246 (2001)
- Guzman LM, "High frequency of p16 promoter methylation in non-small cell lung carcinomas from Chile", Biol Res, 40, pp.365~372 (2007)
- Dominguez G, "Prevalence of aberrant methylation of p14ARF over p16INK4a in some human primary tumors", Mutat Res, 530, pp.9~17 (2003)
- Tanaka R, "Loss of function of p16 gene and prognosis of pulmonary adenocarcinoma", Cancer, 103, pp.608~615 (2005)
- Park G, "Concurrent p16 methylation pattern as an adverse prognostic factor in multiple myeloma: a methylation-specific polymerase chain reaction study using two different primer sets", ANNALS OF HEMATOLOGY, 90, pp.2011(1) (2011), 73~79[DOI]
- Greipp PR, "International staging system for multiple myeloma", J Clin Oncol, 23, pp.3412~3420 (2005)
- Durie BG, "International uniform response criteria for multiple myeloma", Leukemia, 20, pp.1467~1473 (2006)
- Göhring G, "Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome", Blood, 116, pp.3766~3769 (2010)
- Herman JG, "Methylationspecific PCR: a novel PCR assay for methylation status of CpG islands", Proc Natl Acad Sci U S A, 93, pp.9821~9826 (1996)
- Zheng S, "Correlations of partial and extensive methylation at the p14(ARF) locus with reduced mRNA expression in colorectal cancer cell lines and clinicopathological features in primary tumors", Carcinogenesis, 21, pp.2057~2064 (2000)
- Martin P, "Aberrant gene promoter methylation in plasma cell dyscrasias", Exp Mol Pathol, 84, pp.256~261 (2008)
- Ribas C, "p16 gene methylation lacks correlation with angiogenesis and prognosis in multiple myeloma", Cancer Lett, 222, pp.247~254 (2005)
- Yuregir OO, "Detecting methylation patterns of p16, MGMT, DAPK and E-cadherin genes in multiple myeloma patients", Int J Lab Hematol, 32, pp.142~149 (2010)
- Shiraz OB, "Possible down regulation of the p16 gene promoter in individuals with hepatocellular carcinoma", Hepat Mon, 11, pp.719~723 (2011)
- Durie BG, "A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival", Cancer, 36, pp.842~854 (1975)
- Hari PN, "Is the International Staging System superior to the Durie-Salmon staging system? A comparison in multiple myeloma patients undergoing autologous transplant", Leukemia, 23, pp.1528~1534 (2009)
- Harousseau JL, "Multiple myeloma: ESMO clinical recommendations for diagnosis, treatment and follow-up", Ann Oncol, 19(S2), pp.255~257 (2008)
