Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Prevalence of p16 Methylation and Prognostic Factors in Plasma Cell Myeloma at a Single Institution in Korea

  • Kim, Hyunjung (Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Jekar, Dong Wook (Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, Myungshin (Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, Yonggoo (Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Lim, Jihyang (Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Han, Kyungja (Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Min, Chang-Ki (Department of Hematology and Internal Medicine, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • Published : 2013.01.02
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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.

Keywords

References

  1. Ries LAG MD KM, Stinchcomb DG, Howlader N, Horner MJ, Mariotto A, Miller BA, Feuer EJ, Altekruse SF, Lewis DR, Clegg L, Eisner MP, Reichman M, Edwards BK (Eds). SEER Cancer Statistics Review, 1975-2005, National Cancer Institute. http://seer.cancer.gov/csr/1975_2005/ (based on November 2007 SEER data submission, posted to the SEER web site 2008).
  2. McKenna RW, Kyle RA, Kuehl WM, Grogan TM, Harris NL, Coupland RW. Plasma cell neoplasm. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, ed. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed. Lyon: IARC, 2008:200-13.
  3. Brenner H, Gondos A, Pulte D. Expected long-term survival of patients diagnosed with multiple myeloma in 2006-2010. Haematologica 2009;94:270-5. https://doi.org/10.3324/haematol.13782
  4. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin 2008;58:71-96. https://doi.org/10.3322/CA.2007.0010
  5. Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myeome. Blood 2007;109:3489-95. https://doi.org/10.1182/blood-2006-08-040410
  6. BladeJ, Rosinl L, Cibeira MT. Prognostic factors for multiple myeloma in the era of novel agents. Ann Oncol 2008;19(S7):vii117-20. https://doi.org/10.1093/annonc/mdn324
  7. Smadja NV, Bastard C, Brigaudeau C, Leroux D, Fruchart C; Group Fran-cis de Cytogeeique Heatologique. Hypodiploidy is a major prognos-tic factor in multiple myeloma. Blood 2001;98:2229-38. https://doi.org/10.1182/blood.V98.7.2229
  8. Gonzalez-Paz N, Chng WJ, McClure RF, Blood E, Oken MM, Van Ness B, et al. Tumor suppressor p16 methylation in multiple myeloma: biological and clinical implications. Blood 2007;109:1228-32.
  9. Goto T, Mizukami H, Shirahata A, Sakata M, Saito M, Ishibashi K, et al. Aberrant methylation of the p16 gene is frequently detected in advanc-ed colorectal cancer. Anticancer Res 2009;29:275-7.
  10. Ohashi H, Tsushita K, Utsumi M, Shimoyama M, Murate T, Uchida T, et al. Relationship between methylation of the p15 gene and ectopic expression of the EVI-1 gene in myelodysplastic syndromes (MDS). Leukemia 2001;15:990-1. https://doi.org/10.1038/sj.leu.2402138
  11. Guillerm G, Gyan E, Wolowiec D, Facon T, Avet-Loiseau H, Kuliczkowski K, et al. $p16^{INK4a}$ and $p15^{INK4b}$ gene methylations in plasma cells from mo-noclonal gammopathy of undetermined significance. Blood 2001;98: 244-6. https://doi.org/10.1182/blood.V98.1.244
  12. Guzman LM, Koriyama C, Akiba S, Eizuru Y, Castillo D, Corvalan A, et al. High frequency of p16 promoter methylation in non-small cell lung carcinomas from Chile. Biol Res 2007;40:365-72.
  13. Dominguez G, Silva J, Garcia JM, Silva JM, Rodriguez R, Munz C, et al. Prevalence of aberrant methylation of p14ARF over p16INK4a in some human primary tumors. Mutat Res 2003;530:9-17. https://doi.org/10.1016/S0027-5107(03)00133-7
  14. Tanaka R, Wang D, Morishita Y, Inadome Y, Minami Y, Iijima T, et al. Loss of function of p16 gene and prognosis of pulmonary adenocarcinoma. Cancer 2005;103:608-15. https://doi.org/10.1002/cncr.20827
  15. Park G, Kang SH, Lee JH, Suh C, Kim M, Park SM, et al. Concurrent p16 methylation pattern as an adverse prognostic factor in multiple myeloma: a methylation-specific polymerase chain reaction study using two different primer sets. Ann Hematol 2011;90:73-9. https://doi.org/10.1007/s00277-010-1043-9
  16. Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, BladeJ, et al. International staging system for multiple myeloma. J Clin Oncol 2005;23:3412-20. https://doi.org/10.1200/JCO.2005.04.242
  17. Durie BG, Harousseau JL, Miguel JS, BladeJ, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467-73. https://doi.org/10.1038/sj.leu.2404284
  18. Goring G, Michalova K, Beverloo HB, Betts D, Harbott J, Haas OA, et al. Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome. Blood 2010;116:3766-9. https://doi.org/10.1182/blood-2010-04-280313
  19. Herman JG, Graff JR, Myoaen S, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A 1996;93:9821-6. https://doi.org/10.1073/pnas.93.18.9821
  20. Zheng S, Chen P, McMillan A, Lafuente A, Lafuente MJ, Ballesta A, et al. 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 2000;21:2057-64. https://doi.org/10.1093/carcin/21.11.2057
  21. Martin P, Garcia-Cosio M, Santon A, Bellas C. Aberrant gene promoter methylation in plasma cell dyscrasias. Exp Mol Pathol 2008;84:256-61. https://doi.org/10.1016/j.yexmp.2008.02.003
  22. Ribas C, Colleoni GW, Felix RS, Regis Silva MR, Caballero OL, Brait M, et al. p16 gene methylation lacks correlation with angiogenesis and prog-nosis in multiple myeloma. Cancer Lett 2005;222:247-54. https://doi.org/10.1016/j.canlet.2004.09.038
  23. Yuregir OO, Yurtcu E, Kizilkilic E, Kocer NE, Ozdogu H, Sahin FI. Detect-ing methylation patterns of p16, MGMT, DAPK and E-cadherin genes in multiple myeloma patients. Int J Lab Hematol 2010;32:142-9. https://doi.org/10.1111/j.1751-553X.2009.01146.x
  24. Shiraz OB, Galehdari H, Yavarian M, Geramizadeh B. Possible down regulation of the p16 gene promoter in individuals with hepatocellular carcinoma. Hepat Mon 2011;11:719-23. https://doi.org/10.5812/kowsar.1735143X.588
  25. Durie BG and Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975;36:842-54. https://doi.org/10.1002/1097-0142(197509)36:3<842::AID-CNCR2820360303>3.0.CO;2-U
  26. Hari PN, Zhang MJ, Roy V, Peez WS, Bashey A, To LB, et al. Is the International Staging System superior to the Durie-Salmon staging system? A comparison in multiple myeloma patients undergoing autologous trans-plant. Leukemia 2009;23:1528-34. https://doi.org/10.1038/leu.2009.61
  27. Harousseau JL and Dreyling M. Multiple myeloma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2008;19(S2):ii55-7. https://doi.org/10.1093/annonc/mdn012

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