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M.A. Avagnina



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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-035 - Human Papillomavirus Infection in Lung Squamous Cell Carcinoma and Correlation to p16 INK4a Expression from an Argentine Population (ID 9561)

      09:30 - 16:00  |  Author(s): M.A. Avagnina

      • Abstract
      • Slides

      Background:
      Lung cancer is the leading cause of cancer death worldwide. In 1979, Syrjänen suggested a role for human papillomavirus (HPV) infection in bronchial carcinoma. Many studies have found HPV on lung carcinoma, predominantly in squamous cell carcinoma (SCC). There seems to be a geographical factor determining prevalence rates. In Latin America, only 2 studies, altogether including 51 cases of lung SCC, examined this association. However, data from Argentina is lacking. The aim of this study is to asses the incidence of HPV infection in lung SCC of Argentinean population, and to correlate with p16[INK4a ]expression from an Argentine population.

      Method:
      The study was approved by CEMIC’s Ethics Committee. Informed consent was obtained. Materials consisted of formalin-fixed paraffin-embedded (FFPE) tissue from 29 surgically excised and 11 transbronchial biopsies of primary L-SCC evaluated between 2006-2016. HPV Genotyping: On 50μm-thick slides, tumor was microdissected and DNA was extracted (columns method). Wide-spectrum HPV DNA (L1-ORF) was amplified by PCR. Positive specimens were genotyped by PCR for types 16 and 18. Immunohistochemistry: All p16 staining’s were performed on VENTANA BenchMark GX using antibody CINtec® p16. Staining patterns were interpreted on a binary way (positive or negative). Only cases with diffusely intense cytoplasmic and/or nucleic staining on tumor cell (TC) were considered positive. Cases in which the normal bronchial epithelium resulted p16 positive but TC were negative, were also registered.

      Result:
      HPV was isolated in 10/40 cases (25%). The details of HPV infection and the clinicopathological data is depicted on table 1.

      Clinicopathological features of SCC
      HPV positive (n=10) HPV negative (n=30)
      Gender
      Female 5 11
      Male 5 19
      Age
      <50 1 -
      50-60 - 21
      >60 9 9
      Smoking
      Never-smoker - -
      Smoker - -
      Unknown 10 30
      Tumor cell differentiation
      Well 1 -
      Moderate - 10
      Poorly 9 20
      Keratinizing
      Non-keratinizing 9 27
      Keratinizing 1 3
      p16 positive on tumor cellls
      Positive 3 2
      Negative 7 28
      p16 on bronchial epithelium
      Positive 3 2
      Negative 7 28
      HPV type
      HPV 16 3 -
      HPV 18 5 -
      Co-infection HPV 16 and 18 2 -
      Specimen type
      Transbronchial biopsy 3 8
      Surgical excision 7 22


      Conclusion:
      We detected an HPV infection rate of 25%. HPV18 was the common genotype. On 7 cases, normal bronchial epithelium was both p16 and HPV positive, suggesting that adjacent tumor tissue may be HPV infected. p16 should not be used as a surrogate marker for HPV infection, since it is only positive on 60% of cases.

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    P2.01 - Advanced NSCLC (ID 618)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.01-007 - Molecular Characterization of Non-Small Cell Lung Cancers (NSCLC) in Young Patients from an Argentine Population (ID 7951)

      09:00 - 16:00  |  Author(s): M.A. Avagnina

      • Abstract
      • Slides

      Background:
      NSCLC is the leading cause of cancer-related deaths in Argentina. NSCLC is rarely observed in young adults (aged 18-40 years) and presents distinctive molecular characteristics. This study analyzed the prevalence of oncogenic molecular alterations in tumor samples from young adults treated at our institution. Different molecular biology techniques were used and treatment outcomes were reported.

      Method:
      Retrospective observational study of FFPE tumor samples from individuals aged 18-40 years, presenting stage IV lung adenocarcinoma. ALK fusions were studied by IHC (clone-D5F3) and confirmed with FISH-Vysis. The areas selected for molecular studies were micro-dissected, and DNA/RNA were purified. EGFR mutations were studied by Sanger. If available, targeted NGS was done with Colon and Lung. Cancer Research Panel v2 (CLRP) for DNA analysis; and/or Oncomine™ Panel Focus Assay (OFA) for DNA/RNA analysis. Both panels were performed in an Ion 520 chip sequenced in the Ion S5 Next Generation Sequencing Systems. The sequences obtained were analyzed in the Ion Reporter™ Software 5.2.1. The OFA was informed by Ion Torrent™ Oncomine™ Knowledgebase Reporter.

      Result:
      Six patients were included, 5/6 tumors were lung adenocarcinoma and 1/6, poorly differentiated carcinoma. The male:female ratio was 2:1. Median age was 35y (range 32-37) and all subjects had stage IV disease. EGFR and ALK were tested in all patient's samples, and 4/6 had NGS analysis. Five samples (83%) harbored known targetable oncogenic drivers: EGFR sensitizing mutations occurred in 3/5, ALK translocation with KRAS co-mutation in 1/5, and HER2 exon 20 insertions in 1/5. Only one sample without NGS was negative for the studied oncogenes. Targeted therapies were administered to 4/5 patients. Figure 1



      Conclusion:
      Our series shows a high prevalence of known actionable oncogenic drivers in young patients with NSCLC tumor. In this population an extensive molecular profiling of tumors is required to improve the treatment strategy.

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    P2.02 - Biology/Pathology (ID 616)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.02-071 - Prospective Molecular Study of 22 Genes by NGS in Patients with Non-Small Cell Lung Cancer (NSCLC) in Argentina: A Single Institution Experience (ID 7950)

      09:30 - 16:00  |  Author(s): M.A. Avagnina

      • Abstract
      • Slides

      Background:
      Next generation sequencing has contributed to understanding the biology of NSCLC and to improve therapy selection. The prevalence of other oncogenic alterations beyond EGFR, ALK and KRAS in Argentina remains unknown. The aim of this study was to characterize the genomic lanscape of NSCLC tumors from 45 patients in our institution by NGS.

      Method:
      Prospective observational study. We included 45 patients, over 18 years old, with diagnosis of NSCLC and adequate tumor sample. DNA was purified from FFPET samples. Targeted NGS was done with Colon and Lung Cancer Research Panel v2 (Ion Torrent™ AmpliSeq™ technology) for 22 genes with Ion 520 chip, sequenced in Ion S5 Next Generation Sequencing Systems.

      Result:
      Forte five patients were included in the analysis, 19 female (42%) and 26 male (58%). Median age was 57 years old (range 34-89). Most patients had lung adenocarcinoma 43 (96%), 1 squamous (2%) and 1 adenosquamous histology (2%). A total of 28 patients (62%) had stage IV lung cancer, 18% stage III, 4% stage II and 16% stage I. From 43 evaluable samples, 65 mutations were detected: TP53 n=21, KRAS n=20, EGFR n=9, BRAF n=5, MET n=3, ERBB2 n=2, FGFR3 n=2, PI3K n=2, FGFR2 n=1. Of these, 10 are associated with clinical benefit with approved targeted therapies. Two samples had novel EGFR mutations and 2 had EGFR co-activating mutations (Del19 + L858R; and G719C + S768I). KRAS and TP53 co-mutations were present in 50% of KRAS mutant samples. We encountered 26 variants of unknown significance. In our population, 37 samples (86%) had EGFR Q787Q (c.2361G>A) polymorphism.Figure 1



      Conclusion:
      The distribution of oncogene mutations in patients with NSCLC in our institution in Argentina is similar to other western countries with the exception of higher KRAS mutant patients in this cohort. An ongoing larger trial will provide further information for our country and the region.

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