LAUSR

Letter to the Editor The study by Sterlacci et al. reported interesting data correlating MET overexpression and MET gene amplification with clinico-pathological parameters in a large cohort of patients with surgically resected non-small cell lung cancers (NSCLC) [1]. Nevertheless, no data is reported about other oncogenic alterations. As studying many biomarkers became mandatory for the therapeutic management of patients with NSCLC, it could be interesting to evaluate the correlation between MET expression and other biomarkers. In our daily practice, given its potential value as a predictive biomarker for the treatment with monoclonal anti-MET antibody onartuzumab on the one hand and, in the other hand, given the potential clinical response of some patients with NSCLC to crizotinib anti-MET/ALK/ROS1 tyrosine kinase inhibitor therapy, we routinely perform MET immunohistochemistry in tumor samples of patients with advanced NSCLC. Other biomarkers are also analyzed for these patients following our national guidelines about EGFR, KRAS, BRAF mutations, and ALK and ROS1 rearrangements. About MET testing, we use the same SP44-based immunohistochemisty protocol and scoring system used in the MetMAB phase II trial as reported by Sterlacci et al. considering MET positivity as the presence of moderate and/or strong staining intensity in at least 50% of tumor cells (i.e., scores 2+ or 3+ in the MetMAB trial) [2]. To date, we have scored MET expression in 1778 NSCLC samples and concluded in 1019 (57.3%) MET-positive results. Comparing the 1019 MET-positive and the 759 MET-negative samples in our file, we observed a significant difference about the rate of EGFR mutations (12.5 and 7.5% amongMET-positive and MET-negative samples respectively, p = 0.0007). No significant difference was noted about KRAS mutations (32.2 and 27.9%, p = 0.0517), ALK rearrangements (3.6 and 2.8%, p = 0.31), ROS1 rearrangements (0.78 and 0.13%, p = 0.0553), or BRAFmutations (2.9 and 2.1%, p = 0.2734). The pronostic and theranostic relevance of searching for MET overexpression and MET gene amplification in NSCLC remains controversial to date. Trials that focused on targeting MET expressing NSCLC yielded largely negative results, but some impressive responses have been reported in some patients with MET-amplified NSCLC [3]. Notably, in a French nationwide study, among 25 patients with advanced and MET-amplified NSCLC treated by crizotinib, 8 (32%) patients presented a partial response and 7 (25%) had a stable disease. Interestingly, in this French study, patients were initially selected on the basis of MET immunohistochemistry, and only MET-positive patients were further investigated for MET amplification [4]. Other promising responses have also been reported in patients with NSCLC having MET exon 14 alterations, but the place of MET immunohistochemistry as a preselection tool for MET exon 14 mutation analysis remains uncertain [3]. To search for MET alterations is gaining further interest with recent successes of MET-targeted therapies in NSCLC. Beside EGFR, KRAS, BRAF, ALK, ROS1, and * Arnaud Uguen [email protected]