Clinical-Pathological Correlation of KRAS Mutation Status in Metastatic Colorectal Adenocarcinoma

Karen Bento Ribeiro; Karoline Bento Ribeiro; Omar Feres; Jose Joaquim Ribeiro da Rocha; Liane Rapatoni; Sergio Britto Garcia; Alfredo Ribeiro Silva; Gleici da Silva Castro Perdona; Hayala Cristina Cavenague de Souza; Saul Isaac Garrido Santillan; Harley Francisco de Oliveira; Daniela Pretti da Cunha Tirapelli; Fernanda Maris Peria

doi:10.4021/wjon719w

Clinical-Pathological Correlation of KRAS Mutation Status in Metastatic Colorectal Adenocarcinoma

World J Oncol. 2013 Oct;4(4-5):179-187. doi: 10.4021/wjon719w. Epub 2013 Sep 27.

Authors

Affiliations

¹ Division of Clinical Oncology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo-FMRP-USP), Sao Paulo (SP), Brazil.
² Internal Medicine, Federal University of Triangulo Mineiro (Universidade Federal do Triangulo Mineiro - UFTM), Minas Gerais (MG), Brazil.
³ Department of Surgery and Anatomy, FMRP-USP (SP), Brazil.
⁴ Department of Clinical Oncology, FMRF-USP (SP), Brazil.
⁵ Pathology, FMRP-USP (SP), Brazil.
⁶ Computer Science and Computational Mathematics, Department of Social Medicine, FMRP-USP, Brazil.
⁷ Community Health, FMRP-USP, Brazil, BA in Statistics, Federal University of Sao Carlos (Universidade Federal de Sao Carlos - UFSCar), Brazil.
⁸ Gastroenterology Surgeon, Sao Jose General and Maternity Hospital (Hospital e Maternidade Sao Jose), Uberaba, MG, Brazil.
⁹ Radiation Oncology, FMRP-USP (SP), Radiotherapy Service, FMRP-USP (SP), Brazil.
¹⁰ Clinical Oncology, FMRP-USP (SP), Clinical Oncology Service, FMRP-USP (SP), Brazil.

Abstract

Background: KRAS gene mutations play an important role in the carcinogenesis of colorectal tumors. However, studies that have assessed the association between KRAS gene mutation status and disease characteristics report conflicting results. To assess KRAS gene status (mutated or wild-type) and its association with the clinical, epidemiological, and histopathological features of metastatic colorectal adenocarcinoma as well its association with clinical outcomes.

Methods: Cross-sectional descriptive study in which clinical and histopathological data were collected from the medical records of 65 patients diagnosed with metastatic colorectal adenocarcinoma at the Clinical Oncology Service of the Teaching Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo (Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo -HCFMRP-USP) between 2005 and 2012 and analyzed based on their KRAS gene status.

Results: KRAS gene mutations were found in 49.2% of the tumors, and G/A (25.5%) and Gly12Asp (34.37%) were the most frequent mutations. Among the investigated clinical features (gender, ECOG (Eastern Cooperative Oncology Group), histology, degree of cell differentiation, lymph node ratio, primary tumor site, staging, presence of synchronous metastasis, lung metastasis, and liver metastasis), the association between age less than 65 years with KRAS mutation was statistically significant (P = 0.046). KRAS mutation status did not exhibit a significant correlation with the overall survival of the patients (P = 0.078); however, the cases with KRAS mutation exhibited shorter survival. In the multivariate analysis, synchronous metastasis (P = 0.03) and liver metastasis (P = 0.008) behaved as independent factors of poor prognosis relative to the overall survival of the patients.

Conclusion: The KRAS mutation status did not exhibit prognostic value in the investigated sample. Among the older patients (> 65 years old), wild-type KRAS was more frequently observed compared to mutated KRAS.

Keywords: Colon neoplasms; Epidermal growth factor receptor; Pronto-oncogene proteins p21 (ras); Survival analysis; Tumor biological markers.