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S. Nieto



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    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P3.04-047 - Prospective Study of Molecular Markers in Patients with Advanced Lung Adenocarcinoma in CEMIC. Argentina (ID 2449)

      09:30 - 09:30  |  Author(s): S. Nieto

      • Abstract
      • Slides

      Background:
      Lung Cancer is the first cause of cancer related death in Argentina being Adenocarcinoma the most frequent histology. The incidence of EGFR mutations is 13% but there isn’t data regarding other molecular abnormalities. The objective is to study the prevalence of EGFR, BRAF and KRAS mutations together with ALK and MET overexpression in consecutive adult patients with advanced lung adenocarcinoma.

      Methods:
      Pts with tumor biopsy and candidates for treatment who consented were included. Specific sites regarding each gene were analyzed with PCR and Sanger sequencing: KRAS exon2 (G12V/S/D/A/C/R, G13D, V14X, G15X); EGFR exons 18 (G719C/S/A, V689M, E709K/Q, S720P), 19 (deletions and insetions 746-759), 20 (T790M, D700_N771, V769L, S768I,V765A, T783A) and 21 (L858R,L884Q, G863D,N826S, A839T, K864R) and BRAF exon 15 (V600E, D594M,N709K/Q and S720P) and 11 . IH for ALK was performed with 5A4 Mo Ab and CMET with C-12-sc-10 Mo Ab. CMET 2+/3+ and ALK 3+ were considered positive, ALK positive samples were confirmed by FISH.

      Results:
      From May 2012 to December 2014 119 patients signed the informed consent, 107 pts with at least one mutational and/or IH analysis were included and 12 pts were excluded due to other histologies or inadequate material. Median age was 63 years (32-82), male/female 61/46, smoker/former/never 37 (34%)/50 (47%)/20 (19%). Complete mutational and IH analysis was performed in 85 pts(79,5 %), 3 had incomplete analysis (3,75 %) , and 19 only IH (17,75%). Complete molecular testing was achieved in 90% of surgical and 36% of imaging guided biopsies. KRAS was mutated in 18/85 pts (21%): 12 in codon 12 and 6 in codon 13. EGFR was mutated in 15 pts (15%), 11 (13%) harbored EGFR tki responding mutations: 1 exon 18 (E709K), 1 exon 20 (V765A), 4 in exon 21 (3 L858R and 1 G863D) and 5 have exon 19 deletions. Exon 20 insertions (D770_N771 and V774_c775) conferring EGFR tki resistance were detected in 2 patients (2%). One BRAF mutations were detected in exon 11 (G469A). ALK IH was 3+ in 2/107 (2%) and CMET were positive in 57 % (43% 2+ and 14% 3+) of 106 samples tested. In the 85 patiens where all test were performed the prevalence of KRAS mutations was 21 %, EGFR 15 %, BRAF 1,2 % and ALK 2,4 %..

      Conclusion:
      The molecular analysis of multiple molecular markers in lung adenocarcinoma in an academic center in Argetnina is feasible. The amount of tumor obtained from non surgical biopsies is frequently inadequate for full evaluation by this methods. The prevalence of BRAF, KRAS, EGFR mutations and ALK IHC is similar to larger series in other western countries

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