TY - JOUR
T1 - KRAS mutation status is highly homogeneous between areas of the primary tumor and the corresponding metastasis of colorectal adenocarcinomas
T2 - One less problem in patient care
AU - de Macedo, Mariana Petaccia
AU - Melo, Fernanda M.
AU - Ribeiro, Heber Salvador C.
AU - Marques, Marcio C.
AU - Kagohara, Luciane T.
AU - Begnami, Maria Dirlei
AU - Neto, Julio C.
AU - Ribeiro, Júlia S.
AU - Soares, Fernando A.
AU - Carraro, Dirce M.
AU - Cunha, Isabela W.
N1 - Funding Information:
We acknowledge Fundação de Amparo à Pesquisa do Estado de São Paulo FAPESP, grant 2011/08510-2 for financial support and Fundação Antônio Prudente-AC Camargo Cancer Center, São Paulo, SP, Brazil for institutional support. We acknowledge Severino da Silva Ferreira and Carlos Carlos Ferreira Nascimento for support in preparing all of the slides for the experiments.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Colorectal neoplasms
KW - Genetic heterogeneity
KW - Molecular pathology
KW - Molecular sequence data
KW - Precision medicine
KW - RAS protein
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M3 - Article
AN - SCOPUS:85030624117
VL - 7
SP - 1978
EP - 1989
JO - American Journal of Cancer Research
JF - American Journal of Cancer Research
SN - 2156-6976
IS - 9
ER -