title: Bcl-2 and bax expression in advanced non-small cell lung cancer: lack of correlation with chemotherapy response or survival in patients treated with docetaxel plus vinorelbine.
abstract: Surgical series of non-small cell lung cancer (NSCLC) pathologic samples have shown that the expression of the proteins bcl-2 and bax, which regulate cell death, may have prognostic implications. Laboratory data also suggests that these proteins may impact chemotherapy response. In order to determine the rate of bcl-2 and bax expression in advanced NSCLC and assess the impact on chemotherapy response and patient survival, we performed immunohistochemistry on biopsy samples from patients enrolled in a phase I/II trial of vinorelbine plus docetaxel. We chose to study the pathology of patients in this specific trial because both docetaxel and vinorelbine phosphorylate bcl-2 and we hypothesized that this mechanism may affect clinical outcome. The goal of this study was to determine the feasibility of this analysis, and to observe any differences in response rate or survival based on bcl-2 or bax staining results. Unstained slides from paraffin blocks were obtained for 31 patients (55%) on the phase I/II trial. The patient characteristics for this subgroup did not differ significantly from the entire cohort of patients on the trials. Bcl-2 staining was positive in 5/31 samples (16%, 95% CI 3-29%) and bax was positive in 19/28 samples (68%, 95% CI 51-85%). Bcl-2 and bax staining did not correlate with response (p = 0.65 and 1.00 respectively, Fisher's exact test), or survival (by Kaplan-Meier curves). In conclusion, bcl-2 and bax expression was similar in this population with advanced NSCLC to previously reported results for early stage disease, but did not predict response to vinorelbine plus docetaxel in this series.
authors.affiliation: Department of Medicine, Thoracic Oncology Service, Division of Solid Tumor Oncology, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, NY, USA. krugl@mskcc.org
authors.forename: Lee M
authors.initials: LM
authors.lastname: Krug
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Filippa
authors.forename: Ennapadam
authors.initials: E
authors.lastname: Venkatraman
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Ng
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D015331:Cohort Studies; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D008297:Male; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015996:Survival Rate; D043823:Taxoids; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D043823:Taxoids; D051028:bcl-2-Associated X Protein; D000077143:Docetaxel; D014747:Vinblastine; D017239:Paclitaxel; D000077235:Vinorelbine