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G. Fontanini



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    MO16 - Prognostic and Predictive Biomarkers IV (ID 97)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO16.01 - Different Micro-RNA expression in lung adenocarcinoma with molecular driver events (ID 2316)

      16:15 - 17:45  |  Author(s): G. Fontanini

      • Abstract
      • Presentation
      • Slides

      Background
      Oncogenic driver alterations identify several types of lung adenocarcinoma with different prognosis and sensitivity to targeted agents. MicroRNAs (miRNAs) are a new class of non-coding RNAs involved in gene expression regulation. How miRNAs are dysregulated in lung cancer with ALK translocation, EGFR or KRAS mutation is largely unknown. In the present analysis we aimed to investigate miRNAs expression according to a specific molecular driver and to correlate miRNAs deregulation with patient outcome.

      Methods
      The study was conducted in a cohort of 67 lung adenocarcinoma patients (pts) including 17 ALK+ tumors, 11 ALK-/EGFR mutation+, 15 ALK-/KRAS mutation+, 24 ALK-/EGFR and KRAS wild-type and defined as triple negative cases. Matched normal lung tissues from 18 cases representative of the entire cohort were also included onto the analysis. RNA was isolated from formalin-fixed paraffin-embedded tissue (FFPE), using the Recover ALL kit (Ambion). NanoString nCounter system platform was used to generate the miRNA profile. We used Limma to test for differential expression analysis of data. Among the miRNAs evaluated, the miR-515 family expression between tissues was validated by RT-qPCRs, analyzed using the parametric t-test (unpaired, 2-tailed for validation).

      Results
      miRNA expression profile clusters distinctly ALK+ pts from ALK- and normal lung tissue. Within the ALK- group we found specific miRNAs subsets able to sub-stratify KRAS versus EGFR careers clustering sharply triple negative versus EGFR mutation+ and triple negative versus KRAS mutation+. miRNAs belonging to the miR-515 family seems to be the most deregulated in the ALK+ versus ALK-. Although their expression is stably high in normal tissues and ALK+ class, they are highly downregulated in KRAS mutated versus EGFR mutated and versus triple negative (p-value <0.001 for all comparisons).

      Conclusion
      miRNAs profile significantly differs in lung cancer pts with ALK translocation, EGFR mutations and KRAS mutations. Putative targets of deregulated miRNAs are under investigation to better define differences in driver-dependent pathway activation.

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-048 - An extensive analysis on T1aN0 non-small cell lung cancer: from surgery to pathology. (ID 2881)

      09:30 - 16:30  |  Author(s): G. Fontanini

      • Abstract

      Background
      Unfortunately, non-small cell lung cancers are often diagnosed at an advanced stage. Early stage, and particularly T1aN0 NSCLCs, still represent a small percentage of all lung cancers at the moment of diagnosis. Research on early stage lung cancer may lead to discover new molecular insights which, hopefully, will reflect on new treatment opportunities: in particular, MicroRNAs (miRNAs) play a key role in cancer pathogenesis. We retrospectively reviewed our recent experience on surgically resected T1aN0 non small cell lung cancers, focusing on their surgical, histological, and molecular characteristic.

      Methods
      From 2000 to 2010 we operated 114 T1aN0 non small cell lung cancers (81 male and 33 female). Most of them (90; 78,94%) underwent a lobectomy, 11 (9,65%) a segmental resection and in 13 cases (11,40%) a wedge resection; systematic lymphadenectomy was always performed. Operation was performed in 104 (91,23%) cases by thoracotomy (either posterolateral or lateral), 3 (2,63%) by VATS surgery and in 7 (6,14%) cases by robot assisted technique. All specimens were reviewed by two pathologists: 48 (42,10%) were invasive adenocarcinoma, 14 (12,28%) in situ/minimally invasive adenocarcinoma, 51 (44,74%) squamous cell carcinoma and 1 (0,88%) anaplastic carcinoma. Furthermore we evaluated Let-7g, miR-21 and miR-205 expression and their prognostic and predictive value.

      Results
      With a mean follow-up of 67 months, the 5-year overall survival is 75,00%. Recurrence occurred in 25 cases (21,93%), with a average disease-free interval of 26 months: 7 cases had a local recurrence, while 18 patients had distant metastasis. No correlation between survival, the kind of intervention performed, histology and cancer grading was found. Furthermore, maximum diameter of cancer do not affect survival. In average 8 ± 5,5 (range 3-28) lymphnodes were resected in 3 ± 1,3 stations (range 2-7): neither numbers of lymphnodes resected nor number of stations examined affect survival. All MicroRNAs considered were compared to the pathological and clinical variables.

      Conclusion
      T1N0 non small cell lung cancer have a good survival with a low recurrence rate. In our experience histology, grading and the kind of resection (wedge resection and segmentectomy vs lobectomy) do not seem to influence recurrence rate and the prognosis. MicroRNAs tools have a good potential role as prognostic and predictive factors in lung cancer.