Myeloid cell leukemia-1 protein expression and myeloid cell leukemia-1 gene amplification in non small cell lung cancer.

ABSTRACT

BACKGROUND: Myeloid cell leukemia-1 (Mcl-1) is a member of the B-cell lymphoma 2 family known to play a significant role in the regulation of apoptosis. Mcl-1 expression has been studied in nonsmall cell lung cancer (NSCLC) cell lines but has not been previously evaluated as a prognostic factor in clinical samples. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded sections from 119 NSCLC, including 33 squamous cell carcinomas (SCC), 55 adenocarcinomas (AC), and 31 either pure adenocarcinoma in situ (AIS) or AC with lepidic features were immunostained by an automated method with rabbit polyclonal Mcl-1. Cytoplasmic Mcl-1 (cMcl-1) immunoreactivity was scored based on intensity and percentage of positive tumor cells in both tumor and adjacent benign epithelium in each case. MCL1 amplification was determined by hybrid capture-based comprehensive genomic profiling (CGP) on a separate cohort of 9393 NSCLC samples. RESULTS: Intense diffuse cMcl-1 overexpression was noted in 35/119 (29%) tumors overall and correlated with tumor type (52% AIS vs. 31% AC vs. 6% SCC, P < 0.0001), tumor grade (48% grade 1 vs. 14% grade 2 vs. 31% grade 3, P = 0.007), small tumor size (36% ≤3.0 cm vs. 16% >3.0 cm, P = 0.016), and lengthened survival within the AIS subgroup (100% alive vs. 42% expired, P = 0.018) while showing a trend toward correlation with nonrecurrent disease overall (32% nonrecurrent vs. 11% recurrent, P = 0.072) and within the AC subgroup (33% nonrecurrent vs. 0% recurrent, P = 0.092). MCL1 amplification was identified in 569 (6%) of 9393 NSCLC by CGP. CONCLUSIONS: cMcl-1 overexpression appears to occur independently from MCL1 gene amplification in NSCLC and correlates with AIS histologic type, lower tumor grade, smaller tumor size, nonrecurrent disease, and increased survival.