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IMPACT OF KRAS MUTATIONS IN CLINICAL FEATURES IN COLORECTAL CANCER

Renato Morato ZANATTO Gianni SANTOS Júnea Caris OLIVEIRA Eduardo Marcucci PRACUCHO Adauto José Ferreira NUNES Gaspar Jesus LOPES-FILHO Sarhan Sydney SAAD About the authors

ABSTRACT

Background:

KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment.

Aim:

To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated.

Methods:

Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined.

Results:

KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009).

Conclusion:

The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.

HEADINGS:
Colorectal neoplasms; Gene frequency; Mutation

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