Relationship of Amplification and Expression of the C-MYC Gene with Survival among Gastric Cancer Patients

  • Khaleghian, Malihea (Department of Medical Genetics, Iran National Tumor Bank, Cancer Institute of Iran, Tehran University of Medical Sciences) ;
  • Shakoori, Abbas (Department of Medical Genetics, Iran National Tumor Bank, Cancer Institute of Iran, Tehran University of Medical Sciences) ;
  • Razavi, Amirnader Emami (Department of Pathology, Iran National Tumor Bank, Cancer Institute of Iran, Tehran University of Medical Sciences) ;
  • Azimi, Cyrus (Department of Medical Genetics, Iran National Tumor Bank, Cancer Institute of Iran, Tehran University of Medical Sciences)
  • Published : 2015.11.04


Background: During the past decades, the incidence and mortality rate of stomach cancer has demonstrated a great decrease in the world, but it is still one of the most common and fatal cancers especially among men worldwide, including Iran. The MYC proto-oncogene, which is located at 8q24.1, regulates 15% of genes and is activated in 20% of all human tumors. MYC amplification and overexpression of its protein product has been reported in 15-30% of gastric neoplasias. The aim of this investigation was to find the relative efficacy of CISH (chromogenic in situ hybridization) or IHC (immunohistochemistry) in diagnosis and prognosis of gastric cancer, as well as the relationship of amplification and expression of C-MYC gene with patient survival. Materials and Methods: In this cross-sectional study, 102 samples of gastric cancer were collected from patients who had undergone primary surgical resection at the Cancer Institute Hospital, Tehran University of Medical Sciences, from July 2009 to March 2014. All samples were randomly selected from those who were diagnosed with gastric adenocarcinomas. CISH and IHC methods were performed on all of them. Results: Patients were classified into two groups. The first consisted of stage I and II cases, and the second of stage III and IV. Survival tests for both groups was carried out with referrnce to CISH test reults. Group II (stage III & IV) with CISH+ featured lower survival than those with CISH- (p=0.233), but group I (stage I & II) patients demonstrated no significant variation with CISH+ or CISH- (p=0.630). Kaplan-Meier for both groups was carried out with IHC test findings and showed similar results. This data revealed that both diffuse and intestinal types of gastric cancer occurred significantly more in men than women. Our data also showed that CISH+ patients (43%) were more frequent in comparison with IHC+ patients (14.7%). Conclusions: For planning treatment of gastric cancer patients, by focusing on expanding tumors, which is the greatest concern of the surgeons and patients, CISH is a better and more feasible test than IHC, in regard to sensitivity and specificity. Therefore, CISH can be used as a feasible test for tumor growth and prognosis in stage III and IV lesions. This study also indicated that C-MYC amplification in gastric cancer is correlated with survival in advanced stages.


  1. Adhikary S, Eilers M (2005). Transcriptional regulation and transformation by Myc proteins. Nature Rev Mol Cell Biol, 6, 635-45.
  2. Almasi Z, Rafiemanesh H, Salehiniya H (2015). Epidemiology characteristics and trends of incidence and morphology of stomach cancer in Iran. Asian Pac J Cancer Prev, 16, 2757-61.
  3. Altman DG (1990). Practical statistics for medical research, CRC Press.
  4. Arvanitis C, Felsher DW (2005). Conditionally MYC: insights from novel transgenic models. Cancer Letters, 226, 95-9.
  5. Basaran H, Koca T, Cerkesli AK, et al (2015). Treatment outcomes and survival study of gastric cancer patients: a retrospective analysis in an endemic region. Asian Pac J Cancer Prev, 16, 2055-60.
  6. Bener A, Ayub H, Kakil R, et al (2008). Patterns of cancer incidence among the population of Qatar: a worldwide comparative study. Asian Pac J Cancer Prev, 9, 19-24.
  7. Bizari L, Silva AE, Tajara EH (2006). Gene amplification in carcinogenesis. Genet Mol Biol, 29, 1-7.
  8. Bray F, Ren JS, Masuyer E, et al (2013). Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Inter J Cancer, 132, 1133-45.
  9. Brooks-Wilson A, Kaurah P, Suriano G, et al (2004). Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria. J med genet, 41, 508-17.
  10. Calcagno DQ, Leal MF, Takeno SS, et al (2005). Aneuploidy of chromosome 8 and C-MYC amplification in individuals from northern Brazil with gastric adenocarcinoma. Anticancer Res, 25, 4069-74.
  11. Calcagno DQ, Leal MF, Seabra AD, et al (2006). Interrelationship between chromosome 8 aneuploidy, C-MYC amplification and increased expression in individuals from northern Brazil with gastric adenocarcinoma. World J Gastroenterol, 12, 6207.
  12. Calcagno DQ, Leal MF, Assumpcao PP, et al (2008). MYC and gastric adenocarcinoma carcinogenesis. World J Gastroenterol, 14, 5962.
  13. Calcagno DQ, Guimaraes AC, Leal MF, et al (2009). MYC insertions in diffuse-type gastric adenocarcinoma. Anticancer Res, 29, 2479-83.
  14. Calcagno DQ, Freitas VM, Leal MF, et al (2013). MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer. BMC Gastroenterol, 13, 1-10.
  15. Chang MS, Uozaki H, Chong JM, et al (2006). CpG island methylation status in gastric carcinoma with and without infection of Epstein-Barr virus. Clin Can Res, 12, 2995-3002.
  16. Chen XZ, Jiang K, Hu JK, et al (2008). Cost-effectiveness analysis of chemotherapy for advanced gastric cancer in China. World J Gastroenterol, 14, 2715-22.
  17. Cho BY (2014). Evaluation of the validity of current national health screening programs and plans to improve the system. Seoul University, Seoul. pp. 741-58.
  18. Choi JS, Seo J, Jung EJ, et al (2012). C-MYC amplification in mucinous gastric carcinoma: a possible genetic alteration leading to deeply invasive tumors. Anticancer Res, 32, 5031-8.
  19. Chong VH, Telisinghe PU, Abdullah MS, et al (2014). Gastric cancer in brunei darussalam: epidemiological trend over a 27 year period (1986-2012). Asian Pac J Cancer Prev, 15, 7281-5.
  20. Dang CV, O'Donnell KA, Zeller KI, et al (2006). (Editors). The C-MYC target gene network. seminars in cancer biology, elsevier.
  21. Derakhshan M, Yazdanbod A, Sadjadi A, et al (2004). High incidence of adenocarcinoma arising from the right side of the gastric cardia in NW Iran. Gut, 53, 1262-6.
  22. de Souza CRT, Leal MF, Calcagno DQ, et al (2013). MYC deregulation in gastric cancer and its clinicopathological implications. PLOS One, 8, 64420.
  23. Diolaiti D, McFerrin L, Carroll PA, et al (2014). Functional interactions among members of the MAX and MLX transcriptional network during oncogenesis. Bioch Biophy Acta, 1849, 484-500
  24. Fan XM, Wong BCY, Wang WP, et al (2001). Inhibition of proteasome function induced apoptosis in gastric cancer. Inter J Cancer, 93, 481-8.
  25. Fang WL, Chang SC, Lan YT, et al (2013). Molecular and survival differences between familial and sporadic gastric cancers. Biomed Res Int, 2013, 396272.
  26. Ferlay J, Soeriomataram I, Ervik M, et al (2013). Cancer incidence and mortality worldwide: IARC cancerbase, lyon. international agency for research on cancer (iarc). globocan 2012.
  27. Garcia M, Jemal A, Ward EM, et al (2007). Global cancer facts and figures 2007. atlanta, GA: american cancer society.
  28. Hamashima C, Shibuya D, Yamazaki H, et al (2008). The Japanese guidelines for gastric cancer screening. Jpn J Clin Oncol, 38, 259-67.
  29. Hamashima C, Ogoshi K, Okamoto M, et al (2013). A community-based, case-control study evaluating mortality reduction from gastric cancer by endoscopic screening in Japan. PLOS One, 8, 79088.
  30. Hamashima C (2015). Have we comprehensively evaluated the effectiveness of endoscopic screening for gastric cancer? Asian Pac J Cancer Prev, 16, 3591-2.
  31. Hamilton SR, Aaltonen LA (2000). (editors). Pathology and genetics of tumours of the digestive system. the international agency for reseaech on cancer. IARC Press, Lyon.
  32. Han MA, Choi KS, Lee HY, et al (2011). Current status of thyroid cancer screening in Korea: results from a nationwide interview survey. Asian Pac J Cancer Prev, 12, 1657-63.
  33. Han S, Kim HY, Park K, et al (1999). C-MYC expression is related with cell proliferation and associated with poor clinical outcome in human gastric cancer. J Korean Med Sci, 14, 526-30.
  34. Hartgrink HH, Jansen EPM, Van Grieken NCT, et al (2009). Gastric cancer. Lancet, 374, 477-90.
  35. Holian O, Wahid S, Atten MJ, et al (2002). Inhibition of gastric cancer cell proliferation by resveratrol: role of nitric oxide. Am J Physio Gastro Liv Physio, 282, 809-16.
  36. Hundahl SA, Phillips JL, Menck HR (2000). The National Cancer Data Base report on poor survival of US gastric carcinoma patients treated with gastrectomy. Cancer, 88, 921-32.<921::AID-CNCR24>3.0.CO;2-S
  37. Janjigian YY, Tang LH, Coit DG, et al (2011). MET expression and amplification in patients with localized gastric cancer. Cancer Epidemiol Biomarkers Prev, 20, 1021-7.
  38. Jemal A, Bray F, Center MM, et al (2011). Global Cancer Statistics. Ca Cancer J Clin, 61, 69-90.
  39. Lai JF, Kim S, Li C, et al (2008). Clinicopathologic characteristics and prognosis for young gastric adenocarcinoma patients after curative resection. Annals Surg Oncol, 15,1464-9.
  40. Lauren P (1965). The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand, 64, 31-49.
  41. Lin WL, Sun JL, Chang SC, et al (2014). Factors predicting survival of patients with gastric cancer. Asian Pac J Cancer Prev, 15, 5835-8.
  42. Liu X, Cai H, Huang H, et al (2011). The prognostic significance of apoptosis-related biological markers in Chinese gastric cancer patients. PLOS One, 6, 29670.
  43. Louis SF, Vermolen BJ, Garini Y, et al (2005). C-MYC induces chromosomal rearrangements through telomere and chromosome remodeling in the interphase nucleus. Proceedings Nat Acad Sci USA, 102, 9613-8.
  44. Matsui A, Ihara T, Suda H, et al (2013). Gene amplification: mechanisms and involvement in cancer. Bio Mol Concepts, 4, 567-82.
  45. Meyer N, Penn LZ (2008). Reflecting on 25 years with MYC. Nature Rev Cancer, 8, 976-90.
  46. Movahedi M, Afsharfard A, Moradi A, et al (2009). Survival rate of gastric cancer in Iran. J Res Med Sci, 14, 367-73.
  47. Oh MG, Kim JH, Han MA, et al (2014). Family history and survival of patients with gastric cancer: a meta-analysis. Asian Pac J Cancer Prev, 15, 3465-70.
  48. Oliveira C, Seruca R, Carneiro F (2006). Genetics, pathology, and clinics of familial gastric cancer. Inter J Surg Path, 14, 21-33.
  49. Owens SR, Appelman HD (2014). Carcinoma of the Stomach. Atlas of Esophagus and Stomach Pathology. Springer.
  50. Parkin DM, Bray F, Ferlay J, et al (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108.
  51. Rhyu MG, Park WS, Jung YJ, et al (1994). Allelic deletions of MCC/APC and p53 are frequent late events in human gastric carcinogenesis. Gastroenterol, 106, 1584-8.
  52. Robertson EV, Jankowski JA (2008). Genetics of gastroesophageal cancer: paradigms, paradoxes, and prognostic utility. Am J Gastroenterol, 103, 443-9.
  53. Ryan K, Birnie G (1996). Myc oncogenes: the enigmatic family. Biochem J, 314, 713-21.
  54. Sadighi S, Raafat J, Mohagheghi M (2005). Gastric carcinoma: 5 year experience of a single institute. Asian Pac J Cancer Prev, 6, 195-6.
  55. Sadjadi A, Zahedi M, Nouraie M, et al (2007). The first population-based cancer survey in Kerman Province of Iran. Iran J Pub Health, 36, 26-34.
  56. Selcukbiricik F, Tural D, Bilici A, et al (2013). Clinicopathological features and localization of gastric cancers and their effects on survival in Turkey. Asian Pac J Cancer Prev, 14, 553-6.
  57. Shah MA, Ajani JA (2010). Gastric cancer - an enigmatic and heterogeneous disease. JAMA, 303, 1753-4.
  58. Shan Z, Shakoori A, Bodaghi S, et al (2013). TUSC1, a putative tumor suppressor gene, reduces tumor cell growth in vitro and tumor growth in vivo. PLOS One, 8, 66114.
  59. Shon W, Sukov WR, Jenkins SM, et al (2014). MYC amplification and overexpression in primary cutaneous angiosarcoma: a fluorescence in-situ hybridization and immunohistochemical study. Modern Path, 27, 509-15.
  60. Sobin LH, Gospodarowicz MK, Wittekind C, (2011). (editors). TNM classification of malignant tumours. john wiley and sons; New York.
  61. Somi MH, Farhang S, Mirinezhad SK, et al (2008). Cancer in east azerbaijan, Iran: results of a population - based cancer registry. Asian Pac J Cancer Prev, 9, 327-30.
  62. Somi MH, Ghojazadeh M, Bagheri M, et al (2015). Clinicopathological factors and gastric cancer prognosis in the Iranian population: a meta-analysis. Asian Pac J Cancer Prev, 16, 853-7.
  63. Suzuki S, Tenjin T, Watanabe H, et al (1997). Low level C-MYC gene amplification in gastric cancer detected by dual color fluorescence in situ hybridization analysis. J Surg Oncol, 66, 173-8.<173::AID-JSO4>3.0.CO;2-9
  64. Tsuboi K, Hirayoshi K, Takeuchi K, et al (1987). Expression of the C-MYC gene in human gastrointestinal malignancies. Bioch Biophy Res Commu, 146, 699-704.
  65. Valentino C, Kendrick S, Johnson N, et al (2013). Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma. Am J Clin Path, 139, 242-54.
  66. Vita M, Henriksson M, (2006). (editors). The myc oncoprotein as a therapeutic target for human cancer. seminars in cancer biology, elsevier.
  67. Weinberg RA (2008). A biologia do cancer. artmed.
  68. Wong AS, Gumbiner BM (2003). Adhesion-independent mechanism for suppression of tumor cell invasion by E-cadherin. J Cell Biol, 161, 1191-203.
  69. Zhang L, Hou Y, Ashktorab H, et al (2010). The impact of C-MYC gene expression on gastric cancer cell. Mol Cellu Bioch, 344, 125-35.
  70. Zhou YC, Zhao HJ, Shen LZ (2015). Preoperative serum CEA and CA19-9 in gastric cancer - a single tertiary hospital study of 1,075 cases. Asian Pac J Cancer Prev, 16, 2685-91.
  71. Zhu AL, Sonnenberg A (2012). Is gastric cancer again rising? J Clin Gastroenterol, 46, 804-6.

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