Significance of EGFR Protein Expression and Gene Amplification in Non–Small Cell Lung Carcinoma

Abstract

We evaluated epidermal growth factor receptor (EGFR) protein expression by immunohistochemical analysis and EGFR gene amplification by fluorescence in situ hybridization in 199 consecutive newly diagnosed and surgically treated patients with primary non-small cell lung carcinoma (NSCLC) and correlated results with clinicopathologic findings. EGFR protein expression was more common in squamous cell carcinoma (SCC; 17 [26.2%]) than in adenocarcinoma (14 [11.1%]; (P = .0076) and more frequently associated with EGFR amplification (8 [14.5%] vs 4 [3.6%] cases; P = .0208). Poor differentiation was associated with a higher average number of EGFR gene copies per cell (mean, 4.18; P = .0322) and a higher EGFR/chromosome 7 ratio (mean, 1.84; P = .0324). N0 disease showed a higher number of EGFR gene copies (mean, 4.196; P = .0163). SCCs demonstrated a higher EGFR/chromosome 7 ratio than adenocarcinomas (mean, 1.95 vs 1.47; P = .0324), particularly T1 tumors (mean, 1.79; P = .0243). Statistical analysis failed to show correlation between outcome and EGFR protein expression and gene amplification in early NSCLC. EGFR protein expression was uncoupled from gene amplification in most cases, although good correlation occurred in a subset of SCCs.

Salivary gland-type lung carcinomas: an EGFR immunohistochemical, molecular genetic, and mutational analysis study

“…[27][28][29] Although no amplification of EGFR was identified, copy gains of EGFR gene occurred in a quarter of our cases secondarily to polysomy of chromosome 7. This alteration was twice as common in adenoid cystic carcinomas compared to mucoepidermoid carcinomas.…”

“…Indeed, although one study reported no significant prognostic value, 40 increased EGFR gene and chromosome 7 copy numbers were reportedly associated with poor tumor differentiation but were less frequent in T4 compared to T1 tumors. 28 Also, increased EGFR gene and chromosome 7 copy numbers tended to be less frequent in tumors with lymph node metastasis. 28 These results would suggest that chromosome 7 polysomy is associated with lower stage disease, a similar finding to our study, although limited by the small number of cases.…”

“…28 Also, increased EGFR gene and chromosome 7 copy numbers tended to be less frequent in tumors with lymph node metastasis. 28 These results would suggest that chromosome 7 polysomy is associated with lower stage disease, a similar finding to our study, although limited by the small number of cases. Furthermore, a recent study 41 suggested that chromosome 7 polysomy was significantly associated with improved survival in a multivariate analysis of patients with non-small-cell lung carcinoma treated with gefitinib.…”

Chromosome 7 Multiplication in EGFR-positive Lung Carcinomas Based on Tissue Microarray Analysis

“…Several protein and molecular studies have shown that EGFR expression is related to the gene amplification mechanism, but the role of chromosome 7 multiplication is under consideration (33). The significance of the assessment of EGFR gene copy number and EGFR protein expression as biomarkers to predict therapy responders as well as the selection of patients who might potentially benefit from EGFR targeted therapies was demonstrated by different studies (34,35). In fact, data for the relationship between EGFR expression on the protein level and response to EGFR specific therapies is inconsistent (36).…”

Overexpression of EGFR Protein in Bruneian Lung Cancer Patients

“…The correlation between levels of EGFR and treatment effectiveness is debated. Reports of EGFR as a prognostic factor showed disparate results, though for some tumors, EGFR is a good indicator of reduced survival rates in more aggressive disease (Dacic et al, 2006).…”