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

Author(s):Show less -

de Macedo, Mariana Petaccia ^[1] ; Melo, Fernanda M. ^[1] ; Ribeiro, Heber Salvador C. ^[2] ; Marques, Marcio C. ^[2] ; Kagohara, Luciane T. ^[3] ; Begnami, Maria Dirlei ^{[1, 4]} ; Neto, Julio C. ^[4] ; Ribeiro, Julia S. ^[1] ; Soares, Fernando A. ^{[1, 3]} ; Carraro, Dirce M. ^{[1, 4]} ; Cunha, Isabela W. ^{[1, 3]}

Affiliation

^[1] AC Camargo Canc Ctr, Diagnost Mol Pathol Lab, Dept Anat Pathol, Rua Antonio Prudente 211, BR-01509900 Sao Paulo - Brazil

^[2] AC Camargo Canc Ctr, Dept Abdominal Surg, Sao Paulo - Brazil

^[3] AC Camargo Canc Ctr, Lab Investigat Pathol, CIPE, Sao Paulo - Brazil

^[4] AC Camargo Canc Ctr, CIPE, Lab Gen & Mol Biol, Sao Paulo - Brazil

• Document type: Journal article
• Source: AMERICAN JOURNAL OF CANCER RESEARCH; v. 7, n. 9, p. 1978-1989, 2017.
• Web of Science Citations: 4

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 metastatic-remains 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. (AU)

• FAPESP's process: 11/08510-2 - Mutational status of the Kras gene in primary and metastatic colorectal carcinomas
• Grantee: Isabela Werneck da Cunha
• Support Opportunities: Regular Research Grants