KRAS mutation status is highly homogeneous between areas of the primary tumor and the corresponding metastasis of colorectal adenocarcinomas: One less problem in patient care

Mariana Petaccia de Macedo, Fernanda M. Melo, Heber Salvador C. Ribeiro, Marcio C. Marques, Luciane T. Kagohara, Maria Dirlei Begnami, Julio C. Neto, Júlia S. Ribeiro, Fernando A. Soares, Dirce M. Carraro, Isabela W. Cunha

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Mutations in KRAS are negative predictors of the response to anti-EGFR therapies in the treatment of metastatic colorectal cancer. Yet, the ideal tissue to test for KRAS mutation-primary or metastaticremains unknown, as is the validity of testing only 1 area of the primary tumor. The aim of this study was to determine the heterogeneity of KRAS mutational status between areas of the primary lesion and between paired primary CRC and the corresponding lymph node (LN), liver, and lung metastasis with a high-sensitivity sequencing method. Design: DNA from 2 or 3 areas from the primary tumor and 1 area of metastatic tissue was obtained from formalin-fixed paraffin-embedded specimens from 102 metastatic CRC patients. Mutations in KRAS codons 12, 13, and 61 were analyzed by pyrosequencing. Results: Ninety-one cases had DNA extracted from more than 1 area of the primary tumor. Only 1 patient showed intratumor heterogeneity, which involved KRAS mutation type, not KRAS mutational status. We examined KRAS mutations in 97 primaries and matched metastatic samples, recording 2 discordant cases, representing 2.1% of our cohort of matched samples. Conclusion: KRAS status is highly homogeneous throughout primary CRC tumor areas and consistent between the primary tumor and metastatic tissue in the same patient. Our data suggest that testing KRAS mutations in only 1 area of the primary or metastatic tissue is suitable for predicting the response to anti-EGFR treatment and guiding clinical decisions.

Original languageEnglish (US)
Pages (from-to)1978-1989
Number of pages12
JournalAmerican Journal of Cancer Research
Volume7
Issue number9
StatePublished - 2017
Externally publishedYes

Keywords

  • Colorectal neoplasms
  • Genetic heterogeneity
  • Molecular pathology
  • Molecular sequence data
  • Precision medicine
  • RAS protein

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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