[Sampling and search for the EGFR mutation: what's taking, when and how to test?]

Abstract

Since the IPASS study, that has shown a benefit in term of progression-free survival in first line of treatment in non-small cell lung cancer (NSCLC) with activating EGFR mutations, and the restricted prescription of this treatment to the presence of these mutations, the determination of the mutational status has became necessary at the diagnosis. This research study of these mutations, present in about 10% of non-selected NSCLC, has to be preferred in case of clinical factors predictive of mutations (sex, race, tobacco status, adenocarcinoma), but don't have to be exclusive, the correlation between these clinical factors and the presence of the mutations being imperfect. Also, the research study of the EGFR mutations should be performed for patients non eligible for chemotherapy (PS>2). Molecular testing could be performed on biopsies, and also on cytology, knowing that there is a mismatch between the tumor and the metastasis for EGFR status. Samples should be prepared according to standardized protocols, avoiding fixation with Bouin. The gold-standard for molecular testing is still sequencing, but alternative targeted tests (allele-specific PCR...) seem to be more sensitive. Some immunohistochemistry tests are in development for EGFR mutations, but have to be validated on large prospective cohorts. At last, new tumoral sampling have to be performed in case of progression under gefitinib in first line, to look for acquired resistance EGFR mutations, or for other resistance molecular markers (Met amplification).