Despite improvements in the detection and use of
biomarkers, including
epidermal growth factor receptor, ERCC1, and p16, the 5-year survival rate with
non-small cell lung cancer remains at 15%. This suggests that additional
biomarkers are needed to better prognosticate
clinical course and guide therapeutic approaches. Previous studies showed that increased levels of
aspartyl (asparaginyl)-beta-hydroxylase and a highly related molecule, humbug, correlate with
clinical course and survival with hepatic, biliary, pancreatic, and colon
carcinomas. We now characterize the prognostic use of
aspartyl (asparaginyl)-beta-hydroxylase/humbug immunoreactivity in different subtypes of
non-small cell lung cancer. Tissue microarrays including 375
paraffin-embedded non-small cell
lung cancers (195
adenocarcinomas; 18
bronchioloalveolar carcinomas; 113
squamous cell carcinomas; and 49
large cell carcinomas) were immunostained with FB50
monoclonal antibody, which recognizes human
aspartyl (asparaginyl)-beta-hydroxylase/humbug. Immunoreactivity (intensity and distribution) in neoplastic cells were scored under code, and data were subjected to univariate and Cox multivariate analyses, adjusting for age, stage, and treatment. High levels of FB50 immunoreactivity were more often detected in
adenocarcinomas (28% for
adenocarcinoma, 17% for
bronchioloalveolar carcinoma), compared with
squamous cell carcinomas (10%) and
large cell carcinomas (10%). Univariate analysis demonstrated inverse relationships between intensity of FB50 immunoreactivity and survival with
squamous cell carcinoma (P = .004), and a strong trend with respect to
large cell carcinoma (P = .057). Cox multivariate test showed that FB50 immunoreactivity (P = .025), clinical stage (P = .029), and
tumor size (P = .0001) were all independent predictors of survival with
squamous cell carcinoma. High levels of FB50 immunohistochemical staining correlate with poor prognosis in
non-small cell lung cancer, particularly
squamous cell carcinoma subtype. Therefore, FB50 immunoreactivity may be useful in defining patient subsets that are likely to benefit from adjuvant
therapy.