title: Prognostic value of TP53, KRAS and EGFR mutations in nonsmall cell lung cancer: the EUELC cohort.
abstract: Nonsmall cell lung cancer samples from the European Early Lung Cancer biobank were analysed to assess the prognostic significance of mutations in the TP53, KRAS and EGFR genes. The series included 11 never-smokers, 86 former smokers, 152 current smokers and one patient without informed smoking status. There were 110 squamous cell carcinomas (SCCs), 133 adenocarcinomas (ADCs) and seven large cell carcinomas or mixed histologies. Expression of p53 was analysed by immunohistochemistry. DNA was extracted from frozen tumour tissues. TP53 mutations were detected in 48.8% of cases and were more frequent among SCCs than ADCs (p<0.0001). TP53 mutation status was not associated with prognosis. G to T transversions, known to be associated with smoking, were marginally more common among patients who developed a second primary lung cancer or recurrence/metastasis (progressive disease). EGFR mutations were almost exclusively found in never-smoking females (p=0.0067). KRAS mutations were detected in 18.5% of cases, mainly ADC (p<0.0001), and showed a tendency toward association with progressive disease status. These results suggest that mutations are good markers of different aetiologies and histopathological forms of lung cancers but have little prognostic value, with the exception of KRAS mutation, which may have a prognostic value in ADC.
authors.affiliation: International Prevention Research Institute, Lyon, France.
authors.forename: Chiara
authors.initials: C
authors.lastname: Scoccianti
authors.forename: Aurélien
authors.initials: A
authors.lastname: Vesin
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Martel
authors.forename: Magali
authors.initials: M
authors.lastname: Olivier
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brambilla
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Timsit
authors.forename: Luca
authors.initials: L
authors.lastname: Tavecchio
authors.forename: Christian
authors.initials: C
authors.lastname: Brambilla
authors.forename: John K
authors.initials: JK
authors.lastname: Field
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D018773:Genes, erbB-1 / Q000235:genetics*; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D009154:Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012907:Smoking; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins