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  • Title: Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis.
    Author: Hirsch FR, Varella-Garcia M, Bunn PA, Di Maria MV, Veve R, Bremmes RM, Barón AE, Zeng C, Franklin WA.
    Journal: J Clin Oncol; 2003 Oct 15; 21(20):3798-807. PubMed ID: 12953099.
    Abstract:
    PURPOSE: The epidermal growth factor receptor (EGFR) is frequently overexpressed in non-small-cell lung carcinoma (NSCLC), and EGFR inhibitors are promising new therapeutic agents. The molecular mechanisms responsible for EGFR overexpression are poorly understood. MATERIALS AND METHODS: Gene copy number and protein status of EGFR were investigated in microarrayed tumors from 183 NSCLC patients, including squamous cell carcinoma (SCC; 89 patients) and non-SCC (94 patients) histologies. Protein expression was assessed by immunohistochemistry on a scale from 0 to 400 (percentage of positive cells x staining intensity). Gene and chromosome 7 copy numbers were identified by fluorescent in situ hybridization (FISH). RESULTS: EGFR protein overexpression was observed in 62% of the NSCLC (25% scored 201 to 300; 37% scored 301 to 400), more frequently in SCC than non-SCC (82% v 44%; P <.001), and in 80% of the bronchioloalveolar carcinomas. The prevalent FISH patterns were balanced disomy (40%) and trisomy (38%) for EGFR gene and chromosome 7 (40%), whereas balanced polysomy was seen in 13% and gene amplification was seen in 9% of the patients. Gene copy number correlated with protein expression (r = 0.4; P <.001). EGFR overexpression or high gene copy numbers had no significant influence on prognosis. CONCLUSION: EGFR overexpression is frequent in NSCLC, is most prominent in SCC, and correlates with increased gene copy number per cell. High gene copy numbers per cell showed a trend toward poor prognosis. It will be important to evaluate EGFR gene and EGFR protein status and signal protein expression to properly interpret future clinical trials using EGFR inhibitors.
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