title: RAS mutations vary between lesions in synchronous primary colorectal cancer: testing only one lesion is not sufficient to guide anti-EGFR treatment decisions.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil ; Laboratory of Investigative Pathology, CIPE / AC Camargo Cancer Center, São Paulo, Brazil.
authors: Mariana Petaccia
authors: MP
authors: de Macedo
authors: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors: Fernanda Machado
authors: FM
authors: de Melo
authors: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors: Júlia da Silva
authors: Jda S
authors: Ribeiro
authors: Department of Clinical Oncology, AC Camargo Cancer Center, São Paulo, Brazil.
authors: Celso Abdon Lopes
authors: CA
authors: de Mello
authors: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil ; Laboratory of Investigative Pathology, CIPE / AC Camargo Cancer Center, São Paulo, Brazil.
authors: Maria Dirlei Ferreira
authors: MD
authors: de Souza Begnami
authors: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil ; Laboratory of Investigative Pathology, CIPE / AC Camargo Cancer Center, São Paulo, Brazil.
authors: Fernando Augusto
authors: FA
authors: Soares
authors: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil ; Laboratory of Genomics and Molecular Biology, CIPE / AC Camargo Cancer Center, São Paulo, Brazil.
authors: Dirce Maria
authors: DM
authors: Carraro
authors: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil ; Laboratory of Investigative Pathology, CIPE / AC Camargo Cancer Center, São Paulo, Brazil.
authors: Isabela Werneck
authors: IW
authors: da Cunha
keywords: KRAS; NRAS; anti-EGFR treatment; colorectal cancer; synchronic primary colorectal cancer