title: Comprehensive Molecular Analysis of NSCLC; Clinicopathological Associations.
abstract: BACKGROUND
  Selection of NSCLC patients for targeted therapy is currently based upon the presence of sensitizing mutations in EGFR and EML4/ALK translocations. The heterogeneity of molecular alterations in lung cancer has led to the ongoing discovery of potential biomarkers and targets in order to improve survival.
  
  
  OBJECTIVE
  This study aimed to detect alterations in EGFR, KRAS, BRAF, PIK3CA, MET-gene copy number and ALK rearrangements in a large cohort of 956 NSCLC patients of Hellenic origin using highly sensitive techniques and correlations with clinicopathological characteristics.
  
  
  RESULTS
  Mutations were detected in EGFR 10.6% (101 out of 956 samples), KRAS 26.5% (191 out of 720 samples), BRAF 2.5% (12 out of 471 samples), PIK3CA 3.8% (7 out of 184 samples), MET gene amplification was detected in 18% (31 out of 170) and ALK rearrangements in 3.7% (4 out of 107 samples). EGFR mutations were detected in exon 19 (61.4% of mutant cases), exon 21 p.Leu858Arg (19.8%), exon 20 (15.8%), exon 18 (2.9%) and were correlated with gender histology, smoking status and TTF1 staining. p.Thr790Met mutant cases (3.9%) displayed concurrent mutations in exons 19 or 21. Negative TTF-1 staining showed strong negative predictive value for the presence of EGFR mutations. KRAS mutations were associated with histology, the most common mutation being p.Gly12Cys (38%).
  
  
  CONCLUSIONS
  In conclusion, only 89 patients were eligible for EGFR -TKIs and ALK inhibitors therapy, whereas 257 patients showed other alterations, highlighting the necessity for a detailed molecular profiling potentially leading to more efficient individualized therapies for NSCLC patients.
authors.affiliation: First Department of Pathology, Laikon General Hospital, Athens University Medical School, Athens, Greece.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Chatziandreou
authors.affiliation: First Department of Pathology, Laikon General Hospital, Athens University Medical School, Athens, Greece.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Tsioli
authors.affiliation: First Department of Pathology, Laikon General Hospital, Athens University Medical School, Athens, Greece.
authors.forename: Stratigoula
authors.initials: S
authors.lastname: Sakellariou
authors.affiliation: First Department of Pathology, Laikon General Hospital, Athens University Medical School, Athens, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Mourkioti
authors.affiliation: First Department of Pathology, Laikon General Hospital, Athens University Medical School, Athens, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Giannopoulou
authors.affiliation: First Department of Pathology, Laikon General Hospital, Athens University Medical School, Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Levidou
authors.affiliation: First Department of Pathology, Laikon General Hospital, Athens University Medical School, Athens, Greece.
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.affiliation: First Department of Pathology, Laikon General Hospital, Athens University Medical School, Athens, Greece.
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.affiliation: First Department of Pathology, Laikon General Hospital, Athens University Medical School, Athens, Greece.
authors.forename: Angelica A
authors.initials: AA
authors.lastname: Saetta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D058534:Class I Phosphatidylinositol 3-Kinases; D056915:DNA Copy Number Variations; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D014178:Translocation, Genetic; D018631:ras Proteins / Q000235:genetics
chemical_list: D015415:Biomarkers; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins