The Frequency of K-ras Mutation in Colorectal Adenocarcinomas with Absence of Distant Metastasis at Diagnosis

Ebru Demiralay, Yaman Saglam, Gulum Altaca, Banu Bilezikci, Handan Ozdemir

Department of General Surgery, School of Medicine, Baskent University, Istanbul, Turkey.
Department of Pathology, School of Medicine, Baskent University, Istanbul, Turkey.
Medical Genetics Laboratory, Goztepe Park Medical Hospital, Istanbul, Turkey.

DOI: 10.4236/ss.2012.33022                

Abstract

Purpose: K-ras mutations were reported to be in 40% - 60% of patients with sporadic colorectal cancers (CRCs). HER-2/neu oncogene that is important in breast carcinoma was reported in CRCs in several studies. The aims of our study are to determine; the frequency of K-ras mutation in CRC and positivity of HER-2/neu, the relation between K-ras mutation and HER-2/neu positivity, and also the relation between clinicopathological findings with K-ras mutation and HER-2/neu expression. Methods: Total of 35 colon resection specimen from patients without distant metastasis who were operated due to colorectal adenocarcinoma were included in the study. The sections were examined with light microscopy. Vascular and perineural invasions and pericolonic tumor deposits (PCTD) were investigated. HER-2/neu was applied immunohistochemically. DNA sample obtained from tumor paraffin block was screened for presence of 20 mutations in K-ras gene-codon 12, 13, 61 by AutoGenomics and Infinity Analyzer. Results: K-ras gene mutation was detected in 14 of 35 patients (40%). HER-2/neu positivity was detected in 7 cases (28.57%). There was not any significant correlation between HER-2/neu positivity, K-ras gene mutation and clinicopathological findings. There was direct correlation between PCTD and vascular invasion. Conclusions: There was not correlation between K-ras mutation and clinicopathological findings similar to several other studies. The relation between HER-2/neu expression and clinicopathological findings was not found.

Keywords

Colon Adenocarcinoma; K-ras; HER-2/Neu

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	A. S. Sameer, N. A. Chowdhri, S. Abdullah, Z. A. Shah and M. A. Siddiqi, “Mutation Pattern of K-ras Gene in Colorectal Cancer of Kashmir: A Report,” Indian Journal of Cancer, Vol. 46, No. 3, 2009, pp. 219-225. doi:10.4103/0019-509X.52956
[2]	K. S. Al-Kuraya, “KRAS and TP53 Mutations in Colorectal Carcinoma,” Saudi Journal of Gastroenterology, Vol. 15, No. 4, 2009, pp. 217-219. doi:10.4103/1319-3767.56087
[3]	H. J. Andreyev, A. R. Norman, D. Cunningham, et al., “Kirsten Ras Mutations in Patients with Colorectal Cancer: The ‘RASCAL II’ Study,” British Journal of Cancer, Vol. 85, 2001, pp. 692-696. doi:10.1054/bjoc.2001.1964
[4]	R. T. Belly, J. D. Rosenblatt, M. Steinmann, J. Toner, J. Sun, J. Shehadi, J. L. Peacock, R. F. Raubertas, N. Jani and C. K. Ryan, “Detection of Mutated K12-ras in Histologically Negative Lymph Nodes as an Indicator of Poor Prognosis in Stage II Colorectal Cancer,” Clinical Colorectal Cancer, Vol. 1, No. 2, 2001, pp. 110-116. doi:10.3816/CCC.2001.n.011
[5]	J. Brevik, G. I. Meling, A. Spurkland, T. O. Rognum and G. Gaudernack, “K-ras Mutation in Colorectal Cancer: Relations to Patient Age, Sex and Tumour Location,” British Journal of Cancer, Vol. 69, 1994, pp. 367-371. doi:10.1038/bjc.1994.67
[6]	M. Brink, A. F. P. M. de Goeij, P. M. Weijenberg, G. M. J. M. Roemen, M. H. F. M. Lentjes, M. M. M. Pachen, R. A. Goldbohm and P. A. van den Brandt, “K-ras Oncogene mutAtions in Sporadic Colorectal Cancer in the Netherlands Cohort Study,” Carcinogenesis, Vol. 24, No. 4, 2003, pp. 703-710. doi:10.1093/carcin/bgg009
[7]	U. Kressner, J. Bjorheim, S. Westring, S. S. Wahlberg, L. Pahlman, et al., “Ki-ras Mutations and Prognosis in Colorectal Cancer,” European Journal of Cancer, Vol. 34, No. 4, 1998, pp. 518-521. doi:10.1016/S0959-8049(97)10111-3
[8]	S. G. Martinez-Garza, A. Nunez-Salazar, A. L. Calderon-Garciduenas, F. J. Bosques-Padilla, A. Niderhauser-Garcia and H. A. Barrera-Saldana, “Frequency and Clinicopathology Associations of K-ras Mutations in Colorectal Cancer in a Northeast Mexican Population,” Digestive Diseases, Vol. 17, No. 4, 1999, pp. 225-229. doi:10.1159/000016940
[9]	E. Saraga, D. Bautista, G. Dorta, P. Chaubert, P. Martin, et al., “Genetic Heterogeneity in Sporadic Colorectal Adenomas,” The Journal of Pathology, Vol. 181, No. 3, 1997, pp. 281-286. doi:10.1002/(SICI)1096-9896(199703)181:3<281::AID-PATH777>3.0.CO;2-M
[10]	N. Urosevic, K. Krtolica, A. Skaro-Milic, S. Knezevic-Usaj and A. Dujic, “Prevalence of G-to-T Transversions among K-ras Oncogene Mutations in Human Colorectal Tumors in Yugoslavia,” International Journal of Cancer, Vol. 54, No. 2, 1993, pp. 249-254. doi:10.1002/ijc.2910540215
[11]	J. H. J. M. Van Krieken, A. Jung, T. Kirchner, F. Carneiro, R. Seruca, et al., “KRAS Mutation Testing for Predicting Response to Anti-EGFR Therapy for Colorectal Carcinoma: Proposal for an European Quality Assurance Program,” Virchows Archiv, Vol. 453, No. 5, 2008, pp. 417-431. doi:10.1007/s00428-008-0665-y
[12]	Y. X. Zuo, J. Cao, G. S. Zhu, Y. C. Lu, X. K. Zhou and J. Li, “Mutations in Epidermal Growth Factor Receptor and K-ras in Chinese Patients with Colorectal Cancer,” BMC Medical Genetics, Vol. 11, 2010, p. 34. doi:10.1186/1471-2350-11-34
[13]	N. Sharma, M. Saifo, I. R. Tamaskar, et al., “KRAS Status and Clinical Outcome in Metastatic Colorectal Cancer Patients Treated with First-Line Folfox Chemotheraphy,” Journal of Gastrointestinal Oncology, Vol. 1, No. 2, 2010, pp. 90-96.
[14]	W. Kruszewski, R. Kowara, R. Rzepko, et al., “K-RAS Mutation, and Amplification of C-MYC and C-ERBB2 in Colon Adenocarcinoma,” Folia Histochemica et Cytobiologica, Vol. 42, No. 3, 2004, pp. 173-178.
[15]	T. P. Plesec and J. L. Hunt, “KRAS Mutation Testing in Colorectal Cancer,” Advances in Anatomic Pathology, Vol. 16, No. 4, 2009, pp. 196-203. doi:10.1097/PAP.0b013e3181a9d4ed
[16]	D. J. Ahnen, P. Feigl, F. G. Quan, C. Feneglio-Presier, L. C. Lovato, et al., “Ki-ras Mutation and p53 Overeks- pression Predict the Clinical behavior of Colorectal Cancer: A Southwest Oncology Group Study,” Cancer, Vol. 58, 1998, pp. 1149-1158.
[17]	W. S. Samowitz, K. Curtin, D. Schaffer, M. Robertson, M. Leppert and M. L. Slattery, “Relationship of Ki-ras Mutations in Colon Cancers to Tumor Location, Stage and Survival: A Population-Based Study,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 9, 2000, pp. 1193- 1197.
[18]	M. Tanaka, K. Omura, Y. Watanabe, Y. Oda and I. Nakanishi, “Prognostic Factors of Colorectal Cancer: K-ras Mutation, Overexpression of the p53 Protein, and Cell Proferative Activity,” Journal of Surgical Oncology, Vol. 57, No. 1, 1994, pp. 57-64. doi:10.1002/jso.2930570115
[19]	N. S. Goldstein and J. R. Turner, “Pericolonic Tumor Deposits in Patients with T3N+M0 Colon Adenocarcinomas,” Cancer, Vol. 88, No. 10, 2000, pp. 2228-2238. doi:10.1002/(SICI)1097-0142(20000515)88:10<2228::AID-CNCR5>3.0.CO;2-1
[20]	G. Puppa, P. Maisonneuve, A. Sonzogni, M. Masullo, P. Capelli, et al., “Pathological Assessment of Pericolonic Tumor Deposits in Advanced Colonic Carcinoma: Relevance to Prognosis and Tumor Staging,” Modern Pathology, Vol. 20, 2007, pp. 843-855. doi:10.1038/modpathol.3800791
[21]	K. Ghaffarzadegan, N. Sharifi, H. Vosooghynia, et al., “HER2/neu Expression in Colon Adenocarcinoma and Its Correlation with Clinicopathologic Variables,” IJBMS, Vol. 9, No. 1, 2006, pp. 64-69.
[22]	B. Schuell, T. Gruenberger, W. Scheithauer, C. Zielinski and F. Wrba, “HER2/neu Protein Expression in Colorectal Cancer,” BMC Cancer, Vol. 6, 2006, p. 123. doi:10.1186/1471-2407-6-123
[23]	T. Osaka, M. Miyahara, S. Uchino, M. ?nomata, S. Kitano and M. Kabayashi, “Immunohistochemical Study of cerbB-2 Protein in Colorectal Cancer and the Correlation with Patient Survival,” Oncology, Vol. 55, No. 6, 1998, pp. 548-555. doi:10.1159/000011911