title: Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samples of malignant pleural mesothelioma.
abstract: BACKGROUND
  As epidermal growth factor receptor (EGFR) is involved in the pathogenesis of malignant pleural mesotheliomas (MPMs), the anti-EGFR drugs may be effective in treating MPM patients. Mutations of the EGFR gene or its downstream effectors may cause constitutive activation leading to cell proliferation, and the inhibition of apoptosis and metastases. Consequently, molecular profiling is essential for select patients with MPM who may respond to anti-EGFR therapies.
  
  
  METHODS
  After manual macrodissection, genomic DNA was extracted from 77 histological samples of MPM: 59 epithelioid, 10 biphasic, and 8 sarcomatoid. Epidermal growth factor receptor gene mutations were sought by means of real-time polymerase chain reaction (PCR) and direct sequencing, KRAS gene mutations by mutant-enriched PCR, and PIK3CA and BRAF gene mutations by direct sequencing.
  
  
  RESULTS
  Gene mutations were identified in nine cases (12%): five KRAS, three BRAF, and one PI3KCA mutation; no EGFR gene mutations were detected. There was no difference in disease-specific survival between the patients with or without gene mutations (P=0.552).
  
  
  CONCLUSIONS
  Mutations in EGFR downstream pathways are not rare in MPM. Although none of those found in this study seemed to be prognostically significant, they may support a more specific selection of patients for future trials.
authors.affiliation: Unit of Pathology, Department of Health Sciences, University of Eastern Piedmont Amedeo Avogadro, Via Solaroli 17, Novara 28100, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Mezzapelle
authors.forename: U
authors.initials: U
authors.lastname: Miglio
authors.forename: O
authors.initials: O
authors.lastname: Rena
authors.forename: A
authors.initials: A
authors.lastname: Paganotti
authors.forename: S
authors.initials: S
authors.lastname: Allegrini
authors.forename: J
authors.initials: J
authors.lastname: Antona
authors.forename: F
authors.initials: F
authors.lastname: Molinari
authors.forename: M
authors.initials: M
authors.lastname: Frattini
authors.forename: G
authors.initials: G
authors.lastname: Monga
authors.forename: O
authors.initials: O
authors.lastname: Alabiso
authors.forename: R
authors.initials: R
authors.lastname: Boldorini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005557:Formaldehyde; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D016612:Paraffin Embedding; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction; D016707:Tissue Fixation; D014157:Transcription Factors / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D009687:Nuclear Proteins; C503859:PI3KCA protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D005557:Formaldehyde; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
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