Study of C-MYC amplification and expression in Iranian gastric cancer samples using CISH and IHC methods


1 Department of Medical Genetics, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Pathology, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran


Background: Gastric cancer is the fourth most frequent malignancy and the second cause of cancer-related mortality worldwide. It has been suggested that in gastric carcinogenesis, the C-MYC gene has an important function. The objective of this study is to establish the preference of Chromogenic in situ hybridization (CISH) and Immunohistochemistry (IHC) in the diagnosis and prognosis of gastric cancer.
Materials and Methods: Samples comprised of 50 randomly selected patients of whom 40 were male and 10 female. To evaluate the MYC copy number and its protein expression, CISH and IHC analyses were performed for 50 gastric adenocarcinomas, in Iran.
Results: The location of the tumor in 64% of the patients was the fundus, and in 72% of patients, the tumors were of a diffuse type; 22 samples showed no amplification, and 28 samples were with amplification. MYC immunoreactivity was observed in 13 samples. Twelve samples showed both MYC amplification and MYC immunoreactivity. In addition, among the 28 CISH+ samples, 12 samples had positive signals for IHC and 16 samples had negative signals for IHC. A majority of the IHC-negative patients had no amplification, but only one patient with IHC positive had no amplification.
 Our conclusion was that for the management and treatment of gastric cancer, and for special attention of clinicians, for prognosis and tumor progression, the CISH was a better and more feasible test than IHC, in regard to the sensitivity and specificity.


Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0. Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11. Lyon, France: International Agency for Research on Cancer; 2014.  Back to cited text no. 1
Matsuzaka M, Fukuda S, Takahashi I, Shimaya S, Oyama T, Yaegaki M, et al. The decreasing burden of gastric cancer in Japan. Tohoku J Exp Med 2007;212:207-19.  Back to cited text no. 2
Mohagheghi MA, Mosavi-Jarrahi A, Malekzadeh R, Parkin M. Cancer incidence in Tehran metropolis: The first report from the Tehran population-based cancer registry, 1998-2001. Arch Iran Med 2009;12:15-23.  Back to cited text no. 3
Somi MH, Farhang S, Mirinezhad SK, Naghashi S, Seif-Farshad M, Golzari M. Cancer in East Azerbaijan, Iran: Results of a population-based cancer registry. Asian Pac J Cancer Prev 2008;9:327-30.  Back to cited text no. 4
Nardone G. Review article: Molecular basis of gastric carcinogenesis. Aliment Pharmacol Ther 2003;17(Suppl 2):75-81.  Back to cited text no. 5
Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, et al. Treatment of gastric cancer. World J Gastroenterol 2014;20:1635-49.  Back to cited text no. 6
González CA, Sala N, Capellá G. Genetic susceptibility and gastric cancer risk. Int J Cancer 2002;100:249-60.  Back to cited text no. 7
Dang CV. c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol 1999;19:1-11.  Back to cited text no. 8
Sheiness D, Fanshier L, Bishop JM. Identification of nucleotide sequences which may encode the oncogenic capacity of avian retrovirus MC29. J Virol 1978;28:600-10.  Back to cited text no. 9
Battey J, Moulding C, Taub R, Murphy W, Stewart T, Potter H, et al. The human c-myc oncogene: Structural consequences of translocation into the IgH locus in Burkitt lymphoma. Cell 1983;34:779-87.  Back to cited text no. 10
Cole MD, McMahon SB. The Myc oncoprotein: A critical evaluation of transactivation and target gene regulation. Oncogene 1999;18:2916-24.  Back to cited text no. 11
Dang CV, Resar LM, Emison E, Kim S, Li Q, Prescott JE, et al. Function of the c-Myc oncogenic transcription factor. Exp Cell Res 1999;253:63-77.  Back to cited text no. 12
Milne AN, Sitarz R, Carvalho R, Carneiro F, Offerhaus GJ. Early onset gastric cancer: On the road to unraveling gastric carcinogenesis. Curr Mol Med 2007;7:15-28.  Back to cited text no. 13
Calcagno DQ, Leal MF, Taken SS, Assumpção PP, Demachki S, Smith Mde A, et al. Aneuploidy of chromosome 8 and C-MYC amplification in individuals from northern Brazil with gastric adenocarcinoma. Anticancer Res 2005;25:4069-74.  Back to cited text no. 14
Yang GF, Deng CS, Xiong YY, Gong LL, Wang BC, Luo J. Expression of nuclear factor-kappa B and target genes in gastric precancerous lesions and adenocarcinoma: Association with Helicobactor pylori cagA (+) infection. World J Gastroenterol 2004;10:491-6.  Back to cited text no. 15
Calcagno DQ, Leal MF, Seabra AD, Khayat AS, Chen ES, Demachki S, et al. Interrelationship between chromosome 8 aneuploidy, C-MYC amplification and increased expression in individuals from northern Brazil with gastric adenocarcinoma. World J Gastroenterol 2006;12:6207-11.  Back to cited text no. 16
Onoda N, Maeda K, Chung YS, Yano Y, Matsui-Yuasa I, Otani S, et al. Overexpression of c-myc messenger RNA in primary and metastatic lesions of carcinoma of the stomach. J Am Coll Surg 1996;182:55-9.  Back to cited text no. 17
Costa Raiol LC, Figueira Silva EC, Mendes da Fonseca D, Leal MF, Guimarães AC, Calcagno DQ, et al. Interrelationship between MYC gene numerical aberrations and protein expression in individuals from northern Brazil with early gastric adenocarcinoma. Cancer Genet Cytogenet 2008;181:31-5.  Back to cited text no. 18
Xu AG, Li SG, Liu JH, Gan AH. Function of apoptosis and expression of the proteins Bcl-2, p53 and C-myc in the development of gastric cancer. Apoptosis 2001;17:6.  Back to cited text no. 19
Lauren P. 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 1965;64:31-49.  Back to cited text no. 20
Sobin LH, Gospodarowicz MK, Wittekind C, editors. TNM Classification of Malignant Tumours. New York: John Wiley and Sons; 2011.  Back to cited text no. 21
Calcagno DQ, Guimarães AC, Leal MF, Seabra AD, Khayat AS, Pontes TB, et al. MYC insertions in diffuse-type gastric adenocarcinoma. Anticancer Res 2009;29:2479-83.  Back to cited text no. 22
Altman DG. Practical statistics for medical research. London: CRC Press; 1990.  Back to cited text no. 23
de Souza CR, Leal MF, Calcagno DQ, Costa Sozinho EK, Borges Bdo N, Montenegro RC, et al. MYC deregulation in gastric cancer and its clinicopathological implications. PloS One 2013;8:e64420.  Back to cited text no. 24
Chang MS, Uozaki H, Chong JM, Ushiku T, Sakuma K, Ishikawa S, et al. CpG island methylation status in gastric carcinoma with and without infection of Epstein-Barr virus. Clin Cancer Res 2006;12:2995-3002.  Back to cited text no. 25
The International Agency for Research on Cancer. Organization WH. Hamilton SR, Aaltonen LA, editors. Pathology and Genetics of Tumours of the Digestive System. Lyon: IARC Press; 2000. p.  Back to cited text no. 26
Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev Cancer 2008;8:976-90.  Back to cited text no. 27
Calcagno DQ, Leal MF, Assumpcao PP, Smith MA, Burbano RR. MYC and gastric adenocarcinoma carcinogenesis. World J Gastroenterol 2008;14:5962-2.  Back to cited text no. 28
Liu X, Cai H, Huang H, Long Z, Shi Y, Wang Y. The prognostic significance of apoptosis-related biological markers in Chinese gastric cancer patients. PLoS One 2011;6:e29670.  Back to cited text no. 29
Shah MA, Ajani JA. Gastric cancer-an enigmatic and heterogeneous disease. JAMA 2010;303:1753-4.  Back to cited text no. 30
Seidal T, Balaton AJ, Battifora H. Interpretation and quantification of immunostains. Am J Surg Pathol 2001;25:1204-7.  Back to cited text no. 31
Park DI, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK, et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci 2006;51:1371-9.  Back to cited text no. 32
Shan Z, Shakoori A, Bodaghi S, Goldsmith P, Jin J, Wiest JS. TUSC1, a putative tumor suppressor gene, reduces tumor cell growth in vitro and tumor growth in vivo. PLoS One 2013;8:e66114.  Back to cited text no. 33
Calcagno DQ, Freitas VM, Leal MF, de Souza CR, Demachki S, Montenegro R, et al. MYC, FBXW7 and TP53 copy number variation and expression in gastric cancer. BMC Gastroenterol 2013;13:141.  Back to cited text no. 34
Augenlicht LH, Wadler S, Corner G, Richards C, Ryan L, Multani AS, et al. Low-level c-myc amplification in human colonic carcinoma cell lines and tumors: A frequent, p53-independent mutation associated with improved outcome in a randomized multi-institutional trial. Cancer Res 1997;57:1769-75.  Back to cited text no. 35