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V. Minotti

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    P1.02 - Poster Session 1 - Novel Cancer Genes and Pathways (ID 144)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.02-006 - Identification of targetable driver mutations in molecularly selected never smoker lung adenocarcinomas (ID 2970)

      09:30 - 16:30  |  Author(s): V. Minotti

      • Abstract

      Approximately 25% of lung cancers occur in lifelong never smokers. Although no dominant risk factor has been identified yet, the discover of molecular drivers potentially targetable with biological agents, makes lung cancer in never smokers a unique disease, candidate for a personalized therapy. Through the FISH test, we performed a screening for ALK, ROS1, and RET rearrangements, in a highly selected population of lung adenocarcinoma never smoker patients, previously demonstrated to be wild-type for EGFR and K-RAS mutations.

      We collected archived histological material of 28 EGFR and K-RAS wild-type patients (pts), from a 200 never-smoker advanced lung adenocarcinomas database, to be analyzed for the presence of rearrangements in ALK, ROS1 and RET genes. All pts were treated at the Division of Medical Oncology of the S Maria della Misericordia Hospital in Perugia from October 2003 to February 2013. 20 specimens were included in a tissue microarray (TMA) analysis, whereas 8 were screened in separate subset, due to the scarce samples. FISH test was performed using a combination of commercial reagents and custom designed probes. Median overall survival (OS) of mutated pts compared to the pan-negative ones, was evaluated by Cox multivariate analysis.

      Clinicopathological characteristics: among the 28 patients, 27 were never smokers and 1 former light smoker, with a good performance status; 20 (72%) presented with a metastatic disease at diagnosis, 8 (28%) were locally advanced; median age was 56 years-old, with a predominance of female sex (18/28, 64%). All cases were invasive adenocarcinomas and classified into 18 (64%) solid predominant type, 1 (3.5%) mixed acinar/lepidic pattern, 1 (3.5%) papillary, no predominant subtype for 8 (28%) patients, because of unsufficient histological material available. Of the 28 never smoker cases, we identified 7 gene fusions (25%), including 2 pts ALK+ (7.1%), 3 pts ROS1+ (10.7%) and 2 RET+ cases (7.1%), one compatible with KIF5B:RET and other with CCDC6:RET fusion. Median OS for the entire cohort was 24.5 months (mo), 61.2 mo for mutated pts (any rearrangement) vs 24.1 mo for not-mutated, respectively (P = .292).

      Molecularly selected never smoker lung adenorcinomas associates with a high incidence of driver genes mutations and further investigations to confirm our frequencies in larger cohorts are needed. In line with literature data, our findings suggest a different survival outcome among genotypes, and identification of specific subsets in this special population can lead to successful treatment with target therapies.