ERCC1,VEGFR, NF-kB and Gender in Chemotherapy-Treated Advanced Stage NSCLC: An Ongoing Study Report
A Somoza, HX Bui, N Patil, P Pathrose, A Mostafa, MB Rao, M Anderson, N Abdel Karim. VA Medical Center, Cincinnati, OH; University of Cincinnati, Cincinnati, OH
Background: Excision repair cross-complementation group 1 (ERCC1) expression/resistance to cisplatin therapy has been corroborated by studies in patients with advanced non-small cell lung cancer (NSCLC). VEGFR has been studied as prognostic indicator. NF-kB or p65 transcription factor expression is seen in cancers with advanced local growth. Gender may be a prognostic factor in advanced lung cancer. Our aim was to evaluate ERCC1, VEGFR, NF-kB expression, and gender as prognostic indicators in advanced stage NSCLC patients given cisplatin-based and non-cisplatin based therapy.
Design: Advanced stage NSCLC patients from the VAMC and University of Cincinnati were retrospectively reviewed from 1998-2007. We reviewed the tissue sections for adequacy and selected 40 patients treated with cisplatin-based chemotherapy and 10 treated with non-cisplatin based chemotherapy. IHC for ERCC1 (Mouse monoclonal ab- 8F1, Thermo Scientific, 1:200), VEGF-KDR, (rabbit monoclonal 1:200, Cell signaling) and NF-kB (rabbit monoclonal C-20 1:100; SCBT) were independently graded (0 to 2+ for ERCC1; 0 to 3+ for NF-kB and 0 to 2 for VEGFR). ERCC1, VEGFR, NF-kB reactivity were correlated with overall survival (defined as date of diagnosis to time of death from any cause or last follow up (Cox regression model; Kaplan Meier).
Results: Of 40 patients (mean age=64; range: 42-84); treated with cisplatin, ERCC1 negativity was strongly associated with longer survival (p=0.007); high expression of VEGF-KDR receptor showed better overall survival of 14 vs 9.7 months with lower expression, (not reaching statistical significance). NF-kB (p65) showed expression in 4/46 patients (9.9 months survival vs 13 months with no expression). Women (n=8/all cisplatin based therapy) compared to men (n=42) had a statistically significant better median survival of 31.7 compared to 12.5 months (p=0.04).
Conclusions: In advanced stage NSCLC with chemotherapy: 1. ERCC1 decreased expression may predict longer survival following cisplatin-based therapy. 2. Higher expression of VEGFR may have longer overall survival. 3. NF-kB (p65) expression may have shorter survival. 4. Female gender is associated with longer survival. 5. Studies on a larger sample would be warranted to evaluate these trends.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 261, Tuesday Morning