EGFR and KRAS status of primary sarcomatoid carcinomas of the lung: implications for anti-EGFR treatment of a rare lung malignancy.

Full 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.

Author information

Author/s: Italiano, Antoine (A); Cortot, Alexis B (AB); Ilie, Marius (M); Martel-Planche, Ghyslaine (G); Fabas, Thibault (T); Pop, Daniel (D); Mouroux, Jérôme (J); Hofman, Veronique (V); Hofman, Paul (P); Pedeutour, Florence (F);

Affiliation: Laboratory of Solid Tumors Genetics, Nice University Hospital, Nice, France.

Journal and publication information

Publication Type: Journal Article

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Nov; vol 125 (issue 10) : pp 2479-82

Dates: Created 2009/09/28; Completed 2009/11/05;

PMID: 19681124, status: MEDLINE (last retrieval date: 11/5/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Aged
Aged, 80 and over
Carcinosarcoma - genetics; metabolism; secondary
Female
Gene Dosage
Humans
Lung Neoplasms - genetics; metabolism; pathology

Male
Middle Aged
Mutation - genetics
Prognosis
Proto-Oncogene Proteins - genetics
Receptor, Epidermal Growth Factor - genetics; metabolism
ras Proteins - genetics

Associated Chemicals: KRAS protein, human (0) ; Proto-Oncogene Proteins (0) ; Receptor, Epidermal Growth Factor (EC 2.7.1.112) ; EGFR protein, human (EC 2.7.10.1) ; ras Proteins (EC 3.6.5.2)

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