Author of

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  P3.18 - Poster Session 3 - Pathology (ID 177)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12783

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    P3.18-014 - Implementing systematic histological and genotypic re-evaluation of Non Small Cell Lung Cancer (NSCLC) into routine clinical practice: a monocentric study (ID 2691)

    09:30 - 09:30  |  Author(s): S. Izzo
    • Abstract

    Background
    Cancer is a multistep process in which tumor cells progressively harbour genetic alterations that confer growth and spread advantages. These observations are also confirmed in NSCLCs where specific genetic abnormalities are sensitive to the action of targeted drugs, even if secondary mutations could develop conferring drug resistance. Furthermore, in recent studies, histologic and immunophenotypic changes have been described in patients (pts) with a specific molecular alteration re-biopsied after receiving a targeted therapy. This finding suggest the possibility of a "clonal resistance mechanism" in which genetic-similar cell populations had or acquire selective survival features thus escaping the inhibitory drug effect. In the present study histological examination and wide genetic analyses have been performed in tumor tissue sampled both before and after treatment in an unselected NSCLC patient population in order to elucidate progressive clinic-pathological and genetic abnormalities.

    Methods
    NSCLC pts with adequate tissue samples before and after at least one treatment have been evaluated from July 2006 to March 2013, at Department of Oncology of San Luigi Hospital. All had ECOG Performance Status of 0, median age of 51,5 years and IIIA-IV stage at diagnosis. After histological examination, mutational analyses for EGFR, K-RAS, PIK3CA, B-RAF, and HER2 genes were performed using pyrosequencing or RealtimePCR. ALK and c-MET genomic rearrangement were tested by FISH.

    Results
    A total of 24 (12 males and 12 females) pts were collected. Histological diagnoses were re-confirmed in all but one (4%) case in which morphological and immunophenotypical histology of neuroendocrine small cell lung cancer (SCLC) was found. All samples were adequate for molecular analyses. At the first biopsy EGFR activating mutations were 10/24 (42%) and 3/24 (12,5%) were the exon 20 EGFR p.T790M mutation, 2/3 (66%) associated to EGFR activating mutations. At the second biopsy 6/10 (60%) EGFR activating mutations were maintained and no acquired mutations in EGFR wild type pts at first were found at second biopsy. On the other hand, 6/24 (25%) p.T790M mutation were detected at second biopsy, 5/6 (83%) de novo acquired, 1/6 (17%) maintained and only 1/5 (20%) associated to EGFR activating mutations. The patient who acquired SCLC histology, maintained the L858R EGFR activating mutation after treatment with no other acquired mutation. K-RAS mutations were found in 4/24 (16.7%) first biopsies, while 5/24 (21%) were found at the second biopsies. No mutations were found in BRAF, HER2 and PIK3CA genes. ALK rearrangement was assessed in 5/24 (20,8%) patients; otherwise MET amplification was seen in 3/24 (12.5%) cases only 1/3 (30%) in EGFR mutant cases.

    Conclusion
    These preliminary data showed a complex scenario of basal and acquired alterations on tumor tissue before and after treatment highlighting the need of repeated histological and genotypic assessments to guide at the best treatment decisions.