Author of

• 10923

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  P1.18 - Poster Session 1 - Pathology (ID 175)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10944

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    P1.18-021 - Retrospective analysis of the prevalence of NSCLC driver mutations in unselected samples. (ID 3365)

    09:30 - 09:30  |  Author(s): D. Soulieres
    • Abstract

    Background
    Much of the recent improvement in lung cancer outcomes owes to the advent of the Lung Cancer Mutation Consortium. We aimed to assess thequality of the pathologic specimens and to study the prevalence of each of the most clinically relevant driver mutations in a non-referred population with non-squamous, non-small cell lung cancer (NS-NSCLC) treated in a tertiary center in the province of Quebec characterized by a high prevalence of smokers (25% of adult population).

    Methods
    Consecutive patients with pathologically proven NS-NSCLC diagnosed or treated in our institution between January 2006 and June 2009 inclusively were accrued. Patients whose diagnosis is based uniquely on a positive cytology or whose diagnostic material was not available were excluded. Specimens were tested for ALK translocations (by IHC and FISH), for EGFR mutations in exons 19 and 21 by PCR (fragment analysis and qPCR) and for mutations in KRAS codons 12 and 13 by PCR-RFLP. ALK-FISH and ALK-IHC results were analyzed in a blinded manner.

    Results
    A total of 1017 consecutive patients were screened. We excluded 209 patients who had only cytologic material, 55 patients who had no residual material and 197 patients who had insufficient tissue. Analysis was possible on 556 patients. The median age of the analyzed population was 64 years and male gender frequency was 45.5%. Compared to our entire cohort, metastatic cases were significantly under-represented in the analyzed population 27.3% vs. 79.1% for local disease (p<0.0001). The distribution according to stage and year of diagnosis along with that related to overall eligible population as well as the percentage of each of the 3 driver mutations status in the specimens analyzed so far are shown in the table below:

    	Local disease analyzable / overall	Loco-regional analyzable / overall	Metastatic analyzable / overall	Total analyzable / overall
    2006 - 2007	188/227 (82.8%)	66/147 (44.9 %)	55/207 (26.6 %)	311/583 (53.3 %)
    2008 - Mid 2009	161/214 (75.2%)	50/96 (52.1 %)	36/126 (28.6 %)	247/436 (56.7 %)
    Total	349/441 (79.1%)	116/243 (47.7%)	91/333 (27.3 %)	556/1017 (54.7 %)
    Mutation results:	Local disease positive/total analyzed	Loco-regional positive/total analyzed	Metastatic positive/total analyzed	Total positive/total analyzed
    KRAS codon 12	76/216 (35.2%)	20/55 (36.4%)	17/54 (31.5%)	113/325 (34.8%)
    KRAS codon 13	7/216 (3.2%)	2/55 (3.6%)	2/54 (3.7%)	11/325 (3.1%)
    KRAS mutated	83/216 (38.4%)	22/55 (40%)	19/54 (35.2%)	124/325 (37.9%)
    EGFR exon 19	11/128 (8.6%)	2/42 (4.8%)	4/39 (10.3%)	17/209 (8.1%)
    EGFR exon 21	6/128 (4.7%)	3/42 (7.1%)	1/39 (2.6%)	10/209 (4.8%)
    EGFR mutated	17/128 (13.3%)	5/42 (11.9%)	5/39 (12.8%)	27/209 (12.9%)
    ALK-FISH	2/264 (0.8%)	0/90 (0%)	1/69 (1.4%)	3/423 (0.7%)
    ALK – IHC*	1/277 (0.4%)	0/97 (0%)	1/75 (1.3%)	2/453 (0.4%)

    *One ALK-FISH positive case was IHC negative on repeated testing.

    Conclusion
    Our study shows that adequate tumor sampling is a challenge when performing retrospective molecular biology studies, creating a bias of adequate tissue availability in favor of more localized stages of disease. Nonetheless, our study shows a lower percentage of EGFR/ALK mutations and a higher percentage of KRAS mutations than that reported by the LCMC and other groups. This may be related to the non-selected, regional distribution and smoking habits of our study population. Prospective studies on the molecular diagnosis of NS-NSCLC will refine epidemiologic features of the different genetic subtypes of this disease.