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ISRN Surgery  2014 

The Presence of Mutations in the K-RAS Gene Does Not Affect Survival after Resection of Pulmonary Metastases from Colorectal Cancer

DOI: 10.1155/2014/157586

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Abstract:

Introduction. Our objective was to identify mutations in the K-RAS gene in cases of pulmonary metastases from colorectal cancer (CRC) and determine whether their presence was a prognostic factor for survival. Methods. We included all patients with pulmonary metastases from CRC operated on between 1998 and 2010. K-RAS mutations were investigated by direct sequencing of DNA. Differences in survival were explored with the Kaplan-Meier method log-rank tests and multivariate Cox regression analysis. Results. 110 surgical interventions were performed on 90 patients. Factors significantly associated with survival were disease-free interval , age , number of metastases , lymph node involvement , size of the metastases , and previous liver metastasis . Searching in 79 patients, K-RAS mutations were found in 30 cases. We did not find statistically significant differences in survival comparing native and mutated K-RAS. We found a higher rate of lung recurrence and shorter time to recurrence in patients with K-RAS mutations. Gly12Asp mutation was associated with higher recurrence and lower survival . Conclusions. The presence of K-RAS mutations in pulmonary metastases does not affect overall survival but is associated with higher rates of pulmonary recurrence. 1. Introduction In general, the development of cancer is the consequence of a gradual accumulation of genetic alterations. These cause a progressive transformation of normal human cells into malignant cells [1]. The RAS family of genes have the highest known rate of mutations in human cancer, and the aberrant activation of the RAS gene due to a mutation leads to an overexpression of Ras proteins, causing changes in the cells that lead to proliferation, invasion, and metastasis [2]. The conversion of Ras of a protooncogene to an oncogene generally occurs as a consequence of a single mutation in the gene. The mutations are found most often in codon 12 of the gene, followed by condon 13 [3]. In the normal human gene, codon 12 has the sequence CGT that codes for the amino acid glycine (Gly). Any change leading to a loss of the Gly residue at codon 12 may change a normal Ras gene into one that is potentially carcinogenic [3]. Similarly, changes in the Gly residue at codon 13 have the same effect [3]. In recent years, researchers have identified over 20 oncogenes, mutations of which contribute to the occurrence of solid tumours in humans [4]. In colorectal carcinoma, the most common mutations are located in the K-RAS, PIK3CA, BRAF, and N-RAS genes [4]. Recently, Tie reported, in the journal Clinical Cancer

References

[1]  H. Linardou, E. Briasoulis, I. J. Dahabreh et al., “All about KRAS for clinical oncology practice: gene profile, clinical implications and laboratory recommendations for somatic mutational testing in colorectal cancer,” Cancer Treatment Reviews, vol. 37, no. 3, pp. 221–233, 2011.
[2]  K. Giehl, “Oncogenic Ras in tumour progression and metastasis,” Biological Chemistry, vol. 386, no. 3, pp. 193–205, 2005.
[3]  E. Vakiani and D. B. Solit, “KRAS and BRAF: drug targets and predictive biomarkers,” Journal of Pathology, vol. 223, no. 2, pp. 219–229, 2011.
[4]  J. Tie, L. Lipton, J. Desai et al., “KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer,” Clinical Cancer Research, vol. 17, no. 5, pp. 1122–1130, 2011.
[5]  T. Kobunai, Y. Yamamoto, K. Matsuda et al., “Heterogeneity of KRAS status may explain the subset of discordant KRAS status between primary and metastatic colorectal cancer,” Diseases of the Colon and Rectum, vol. 54, no. 9, pp. 1170–1178, 2011.
[6]  N. Knijn, L. J. M. Mekenkamp, M. Klomp et al., “KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients,” British Journal of Cancer, vol. 104, no. 6, pp. 1020–1026, 2011.
[7]  J. Pfannschmidt, H. Dienemann, and H. Hoffmann, “Surgical resection of pulmonary metastases from colorectal cancer: a systematic review of published series,” Annals of Thoracic Surgery, vol. 84, no. 1, pp. 324–338, 2007.
[8]  M. Gonzalez, J. H. Robert, N. Halkic et al., “Survival after lung metastasectomy in colorectal cancer patients with previously resected liver metastases,” World Journal of Surgery, vol. 36, no. 2, pp. 386–391, 2012.
[9]  S. Salah, K. Watanabe, S. Welter, et al., “Colorectal cancer pulmonary oligometastases: pooled analysis and construction of a clinical lung metastasectomy prognostic model,” Annals of Oncology, vol. 23, no. 10, pp. 2649–2655, 2012.
[10]  U. Landes, J. Robert, T. Perneger et al., “Predicting survival after pulmonary metastasectomy for colorectal cancer: previous liver metastases matter,” BMC Surgery, vol. 10, article 17, 2010.
[11]  M. Riquet, C. Foucault, A. Cazes et al., “Pulmonary resection for metastases of colorectal adenocarcinoma,” Annals of Thoracic Surgery, vol. 89, no. 2, pp. 375–380, 2010.
[12]  J. Zabaleta, B. Aguinagalde, M. Fuentes, J. M. Izquierdo, C. Hernández, and J. I. Emparanza, “Revisión y actualización de los factores pronósticos de las metástasis pulmonares,” Cirugía Espa?ola, vol. 89, no. 4, pp. 243–248, 2011.
[13]  J. Zabaleta, B. Aguinagalde, M. G. Fuentes et al., “Survival after lung metastasectomy for colorectal cancer: importance of previous liver metastasis as a prognostic factor,” European Journal of Surgical Oncology, vol. 37, no. 9, pp. 786–790, 2011.
[14]  H. Linardou, I. J. Dahabreh, D. Kanaloupiti et al., “Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer,” The Lancet Oncology, vol. 9, no. 10, pp. 962–972, 2008.
[15]  Y. Ward, W. Wang, E. Woodhouse, I. Linnoila, L. Liotta, and K. Kelly, “Signal pathways which promote invasion and metastasis: critical and distinct contributions of extracellular signal-regulated kinase and Ral-specific guanine exchange factor pathways,” Molecular and Cellular Biology, vol. 21, no. 17, pp. 5958–5969, 2001.
[16]  J. S. Ross, “Clinical implementation of KRAS testing in metastatic colorectal carcinoma: the pathologist's perspective,” Archives of Pathology & Laboratory Medicine, vol. 136, no. 10, pp. 1298–1307, 2012.
[17]  C. P. Vaughn, S. D. Zobell, L. V. Furtado, C. L. Baker, and W. S. Samowitz, “Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer,” Genes Chromosomes and Cancer, vol. 50, no. 5, pp. 307–312, 2011.
[18]  P. Cejas, M. López-Gómez, C. Aguayo et al., “KRAS mutations in primary colorectal cancer tumors and related metastases: a potential role in prediction of lung metastasis,” PLoS ONE, vol. 4, no. 12, Article ID e8199, 2009.
[19]  N. Sharma, M. Saifo, I. R. Tamaskar, R. Bhuvaneswari, T. Mashtare, and M. Fakih, “KRAS status and clinical outcome in metastatic colorectal cancer patients treated with first-line FOLFOX chemotherapy,” Journal of Gastrointestinal Oncology, vol. 1, no. 2, pp. 90–96, 2010.
[20]  A. Lamy, F. Blanchard, F. Le Pessot et al., “Metastatic colorectal cancer KRAS genotyping in routine practice: results and pitfalls,” Modern Pathology, vol. 24, no. 8, pp. 1090–1100, 2011.
[21]  N. Moosmann, L. F. von Weikersthal, U. Vehling-Kaiser et al., “Cetuximab plus capecitabine and irinotecan compared with cetuximab plus capecitabine and oxaliplatin as first-line treatment for patients with metastatic colorectal cancer: AIO KRK-0104—a randomized trial of the German AIO CRC study group,” Journal of Clinical Oncology, vol. 29, no. 8, pp. 1050–1058, 2011.
[22]  T. E. Stinchcombe and C. J. Der, “Are all KRAS mutations created equal?” The Lancet Oncology, vol. 12, no. 8, pp. 717–718, 2011.
[23]  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, pp. 692–696, 2001.
[24]  D. P. Modest, A. Jung, N. Moosmann et al., “The influence of KRAS and BRAF mutations on the efficacy of cetuximab-based first-line therapy of metastatic colorectal cancer: an analysis of the AIO KRK-0104-trial,” International Journal of Cancer, vol. 131, no. 4, pp. 980–986, 2012.

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