Amplification and overexpression of the cyclin D1 and epidermal growth factor receptor genes in non-small-cell lung cancer

Purpose: To study the structure and expression of the cyclin D1 and the epi dermal growth factor receptor (EGFR) genes in a cohort of 298 non-small-cel l lung cancer (NSCLC) specimens. Methods: Gene structure was studied by Sou thern analysis, and gene expression was studied by Northern analysis and im munohistochemical analysis. Results: Amplification of the cyclin D1 locus w as found in 14/298 (5%) specimens. All 12/12 specimens with amplification o f the cyclin D1 gene for which RNA was available were found to express the cyclin D1 transcript, and 11/12 overexpressed the transcript to levels high er than that of uninvolved lung. The EGFR gene was amplified in 17/286 samp les of NSCLC tested, and was overexpressed in 22/169 (13%) cases tested, in cluding 12/13 cases with amplification of the gene for which RNA was availa ble. Cyclin D1 gene amplification was associated with advanced lymph node i nvolvement (P = 0.043), but not with larger tumor size or adverse outcome. Cyclin D1 gene amplification and overexpression occurred independently of r etinoblastoma tumor-suppressor gene (RB) inactivation, but tumors with ampl ification of the cyclin D1 gene were more likely to have EGFR gene amplific ation (P < 0.005). No correlation of EGFR gene amplification or overexpress ion with tumor size, lymph node involvement, patient demographic data, or s urvival was identified. Conclusions: These data indicate that the cyclin D1 and EGFR genes are amplified and overexpressed in NSCLC, and amplification of the cyclin D1 gene occurs frequently in conjunction with amplification of the EGFR gene.