Cargando…

RAS mutations vary between lesions in synchronous primary colorectal cancer: testing only one lesion is not sufficient to guide anti-EGFR treatment decisions

INTRODUCTION: Mutations in KRAS and NRAS genes are negative predictors of anti-EGFR therapies response in metastatic colorectal cancer. There are few reports on RAS testing in synchronous primary colorectal cancer (SP-CRC) and a lack of recommendations on which tissue should be tested for the mutati...

Descripción completa

Detalles Bibliográficos
Autores principales: de Macedo, Mariana Petaccia, de Melo, Fernanda Machado, Ribeiro, Júlia da Silva, de Mello, Celso Abdon Lopes, de Souza Begnami, Maria Dirlei Ferreira, Soares, Fernando Augusto, Carraro, Dirce Maria, da Cunha, Isabela Werneck
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381705/
https://www.ncbi.nlm.nih.gov/pubmed/25859555
_version_ 1782364504093360128
author de Macedo, Mariana Petaccia
de Melo, Fernanda Machado
Ribeiro, Júlia da Silva
de Mello, Celso Abdon Lopes
de Souza Begnami, Maria Dirlei Ferreira
Soares, Fernando Augusto
Carraro, Dirce Maria
da Cunha, Isabela Werneck
author_facet de Macedo, Mariana Petaccia
de Melo, Fernanda Machado
Ribeiro, Júlia da Silva
de Mello, Celso Abdon Lopes
de Souza Begnami, Maria Dirlei Ferreira
Soares, Fernando Augusto
Carraro, Dirce Maria
da Cunha, Isabela Werneck
author_sort de Macedo, Mariana Petaccia
collection PubMed
description INTRODUCTION: Mutations in KRAS and NRAS genes are negative predictors of anti-EGFR therapies response in metastatic colorectal cancer. There are few reports on RAS testing in synchronous primary colorectal cancer (SP-CRC) and a lack of recommendations on which tissue should be tested for the mutation in this disease. This study analyzed the RAS status of both lesions in SP-CRC patients and in their metastasis. MATERIALS AND METHODS: DNA was obtained from formalin-fixed-paraffin-embedded tissue, and mutations were analyzed by pyrosequencing. RESULTS: RAS status was heterogeneous in 6 (75%) of 8 SP-CRC patients between primary lesions. Five showed heterogeneity regarding RAS mutational status, and from these, four presented with metastasis: 3 cases (75%) had WT metastatic tissue, and 1 case (25%) had mutated metastatic tissue. One patient showed divergence regarding RAS mutation type. DISCUSSION: RAS mutations vary significantly between SP-CRC lesions, and the status of the metastasis is unpredictable. Testing for RAS mutations in only 1 of the primary lesions can misguide clinical decisions and hind the predictive potential of anti-EGFR treatment. A more appropriate approach in metastatic SP-CRC is to test the metastatic tissue or both primary lesions for providing more accurate mutation scenery and support more assertive clinical decisions.
format Online
Article
Text
id pubmed-4381705
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-43817052015-04-09 RAS mutations vary between lesions in synchronous primary colorectal cancer: testing only one lesion is not sufficient to guide anti-EGFR treatment decisions de Macedo, Mariana Petaccia de Melo, Fernanda Machado Ribeiro, Júlia da Silva de Mello, Celso Abdon Lopes de Souza Begnami, Maria Dirlei Ferreira Soares, Fernando Augusto Carraro, Dirce Maria da Cunha, Isabela Werneck Oncoscience Research Paper INTRODUCTION: Mutations in KRAS and NRAS genes are negative predictors of anti-EGFR therapies response in metastatic colorectal cancer. There are few reports on RAS testing in synchronous primary colorectal cancer (SP-CRC) and a lack of recommendations on which tissue should be tested for the mutation in this disease. This study analyzed the RAS status of both lesions in SP-CRC patients and in their metastasis. MATERIALS AND METHODS: DNA was obtained from formalin-fixed-paraffin-embedded tissue, and mutations were analyzed by pyrosequencing. RESULTS: RAS status was heterogeneous in 6 (75%) of 8 SP-CRC patients between primary lesions. Five showed heterogeneity regarding RAS mutational status, and from these, four presented with metastasis: 3 cases (75%) had WT metastatic tissue, and 1 case (25%) had mutated metastatic tissue. One patient showed divergence regarding RAS mutation type. DISCUSSION: RAS mutations vary significantly between SP-CRC lesions, and the status of the metastasis is unpredictable. Testing for RAS mutations in only 1 of the primary lesions can misguide clinical decisions and hind the predictive potential of anti-EGFR treatment. A more appropriate approach in metastatic SP-CRC is to test the metastatic tissue or both primary lesions for providing more accurate mutation scenery and support more assertive clinical decisions. Impact Journals LLC 2015-02-09 /pmc/articles/PMC4381705/ /pubmed/25859555 Text en Copyright: © 2015 de Macedo et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
de Macedo, Mariana Petaccia
de Melo, Fernanda Machado
Ribeiro, Júlia da Silva
de Mello, Celso Abdon Lopes
de Souza Begnami, Maria Dirlei Ferreira
Soares, Fernando Augusto
Carraro, Dirce Maria
da Cunha, Isabela Werneck
RAS mutations vary between lesions in synchronous primary colorectal cancer: testing only one lesion is not sufficient to guide anti-EGFR treatment decisions
title RAS mutations vary between lesions in synchronous primary colorectal cancer: testing only one lesion is not sufficient to guide anti-EGFR treatment decisions
title_full RAS mutations vary between lesions in synchronous primary colorectal cancer: testing only one lesion is not sufficient to guide anti-EGFR treatment decisions
title_fullStr RAS mutations vary between lesions in synchronous primary colorectal cancer: testing only one lesion is not sufficient to guide anti-EGFR treatment decisions
title_full_unstemmed RAS mutations vary between lesions in synchronous primary colorectal cancer: testing only one lesion is not sufficient to guide anti-EGFR treatment decisions
title_short RAS mutations vary between lesions in synchronous primary colorectal cancer: testing only one lesion is not sufficient to guide anti-EGFR treatment decisions
title_sort ras mutations vary between lesions in synchronous primary colorectal cancer: testing only one lesion is not sufficient to guide anti-egfr treatment decisions
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381705/
https://www.ncbi.nlm.nih.gov/pubmed/25859555
work_keys_str_mv AT demacedomarianapetaccia rasmutationsvarybetweenlesionsinsynchronousprimarycolorectalcancertestingonlyonelesionisnotsufficienttoguideantiegfrtreatmentdecisions
AT demelofernandamachado rasmutationsvarybetweenlesionsinsynchronousprimarycolorectalcancertestingonlyonelesionisnotsufficienttoguideantiegfrtreatmentdecisions
AT ribeirojuliadasilva rasmutationsvarybetweenlesionsinsynchronousprimarycolorectalcancertestingonlyonelesionisnotsufficienttoguideantiegfrtreatmentdecisions
AT demellocelsoabdonlopes rasmutationsvarybetweenlesionsinsynchronousprimarycolorectalcancertestingonlyonelesionisnotsufficienttoguideantiegfrtreatmentdecisions
AT desouzabegnamimariadirleiferreira rasmutationsvarybetweenlesionsinsynchronousprimarycolorectalcancertestingonlyonelesionisnotsufficienttoguideantiegfrtreatmentdecisions
AT soaresfernandoaugusto rasmutationsvarybetweenlesionsinsynchronousprimarycolorectalcancertestingonlyonelesionisnotsufficienttoguideantiegfrtreatmentdecisions
AT carrarodircemaria rasmutationsvarybetweenlesionsinsynchronousprimarycolorectalcancertestingonlyonelesionisnotsufficienttoguideantiegfrtreatmentdecisions
AT dacunhaisabelawerneck rasmutationsvarybetweenlesionsinsynchronousprimarycolorectalcancertestingonlyonelesionisnotsufficienttoguideantiegfrtreatmentdecisions