RAS mutations vary between lesions in synchronous primary Colorectal Cancer: Testing only one lesion is not sufficient to guide anti-EGFR treatment decisions.

Mariana Petaccia de Macedo1,2, Fernanda Machado de Melo1, Júlia da Silva Ribeiro1, Celso Abdon Lopes de Mello3, Maria Dirlei Ferreira de Souza Begnami1,2, Fernando Augusto Soares1,2, Dirce Maria Carraro1,4 and Isabela Werneck da Cunha1,2

1 Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil

2 Laboratory of Investigative Pathology, CIPE / AC Camargo Cancer Center, São Paulo, Brazil

3 Department of Clinical Oncology, AC Camargo Cancer Center, São Paulo, Brazil

4 Laboratory of Genomics and Molecular Biology, CIPE / AC Camargo Cancer Center, São Paulo, Brazil


Mariana Petaccia de Macedo, email:

Keywords: synchronic primary colorectal cancer; colorectal cancer, KRAS, NRAS, anti-EGFR treatment

Received: October 16, 2014 Accepted: Febraury 06, 2015 Published: Febraury 09, 2015


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.

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