Clinicopathologic features and prognostic implications of epidermal growth factor receptor (EGFR) gene copy number and protein expression in non-small cell lung cancer.
Increased epidermal growth factor receptor (EGFR) gene copy numbers and mutations predict sensitivity to EGFR tyrosine kinase inhibitor in non-small cell lung cancer (NSCLC). However, the clinicopathologic features of EGFR gene copy status in NSCLC remain unclear. We retrospectively analyzed 262 cases of NSCLC, including 135 squamous cell carcinomas (SCC) and 112 adenocarcinomas (ADC), for which paraffin blocks of the resected primary lung mass were available. None had received EGFR-targeted therapy. EGFR gene copy number was evaluated using fluorescence in situ hybridization (FISH), and EGFR expression was determined immunohistochemically using a tissue microarray. A high EGFR gene copy (EGFR FISH-positive) was found in 30.2% of the cases (amplification in 11.1% and high polysomy in 19.1%). There was no significant difference in EGFR FISH status with respect to SCC and ADC histology. The EGFR FISH-positive rate was higher in non-smokers than in smokers in the multivariate analysis (p=0.012). EGFR expression was significantly associated with a high EGFR gene copy and SCC histology (p=0.000). In the univariate survival analysis, EGFR FISH-positivity predicted worse survival in SCC (p=0.059), especially stage I SCC (p=0.04). EGFR amplification was associated with a shorter survival in node-positive SCC (p=0.015). However, the EGFR gene copy number or protein expression had no influence on the prognosis of ADC. In conclusion, the EGFR FISH-positive rate in Korean patients with NSCLC was similar to rates in Western populations, unlike the higher frequencies of EGFR mutation in East Asians. A high EGFR gene copy number was significantly more common in non-smokers, as were EGFR mutations. A high EGFR gene copy number predicted worse survival in SCC; therefore, the prognostic implications of the EGFR gene and protein should be analyzed in the context of histology and staging in NSCLC.
Jeon
Yoon Kyung
YK
Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea. junarplus@chol.com <junarplus@chol.com>
Sung
Sook-Whan
SW
Chung
Jin-Haeng
JH
Park
Weon-Seo
WS
Seo
Jeong-Wook
JW
Kim
Chul Woo
CW
Chung
Doo Hyun
DH
D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D018628:Gene Dosage; D018773:Genes, erbB-1; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D014176:Protein Biosynthesis; D016019:Survival Analysis
D004273:DNA, Neoplasm; D066246:ErbB Receptors