title: EGFR and KRAS status of primary sarcomatoid carcinomas of the lung: implications for anti-EGFR treatment of a rare lung malignancy.
abstract: Sarcomatoid carcinomas (SC) of the lung are uncommon malignant tumors composed of carcinomatous and sarcomatous cell components and characterized by a more aggressive outcome than other histological subtypes of nonsmall cell lung cancer (NSCLC). Although epidermal growth factor receptor (EGFR)-targeted therapies have emerged as a promising therapeutic approach in patients with advanced typical NSCLC such as adenocarcinoma, the potential clinical activity of these drugs in lung SC is still unknown. To investigate this point, we have analyzed the status of 4 EGFR pathways biomarkers in a series of lung SC. EGFR protein expression, EGFR gene copy number, EGFR mutational status and KRAS mutational status were assessed in a series of 22 consecutive cases of primary lung SC. EGFR protein overexpression was observed in all the cases. High level of polysomy (>or=4 copies of the gene in >40% of cells) was detected in 5 cases (23%). No EGFR mutation was detected. KRAS mutations were found in 8 patients (38%; Gly12Cys in 6 cases and Gly12Val in 2 cases). The consistent EGFR protein overexpression and the high rate of KRAS mutation may contribute to the poorer outcome of lung SC in comparison with typical NSCLC. The rare incidence of increased EGFR gene copy number, the lack of EGFR mutation and the high rate of KRAS mutation observed in our series also suggest that most patients with lung SC are not likely to benefit from anti-EGFR therapies.
authors.affiliation: Laboratory of Solid Tumors Genetics, Nice University Hospital, Nice, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Italiano
authors.forename: Alexis B
authors.initials: AB
authors.lastname: Cortot
authors.forename: Marius
authors.initials: M
authors.lastname: Ilie
authors.forename: Ghyslaine
authors.initials: G
authors.lastname: Martel-Planche
authors.forename: Thibault
authors.initials: T
authors.lastname: Fabas
authors.forename: Daniel
authors.initials: D
authors.lastname: Pop
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mouroux
authors.forename: Veronique
authors.initials: V
authors.lastname: Hofman
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
authors.forename: Florence
authors.initials: F
authors.lastname: Pedeutour
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002296:Carcinosarcoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins