Abstract
Background
The clinical association between alpha-1 antitrypsin (AAT) blood concentration and phenotypes with non-small cell lung cancer (NSCLC) is not clear, as well as the role of AAT in lung carcinogenesis. We investigated AAT serum levels, phenotypes and protein expression in tumor tissue from NSCLC patients to evaluate its potential biological and clinical significance.
Methods
Serum samples from 148 NSCLC patients (stages I-IV) were analyzed for AAT blood concentration by nephelometry, AAT phenotype by isoelectrofocusing and genotype by DNA sequencing. FFPE tumor tissue samples were stained by immunohistochemistry (IHC) using anti-AAT antibody. Reference group consisted of 154 PiMM COPD patients.
Results
Totally 6/148 (4%) NSCLC patients carried deficient AAT allele (3 MS, 1 MZ, 1 FM, 1 MX) with mean AAT blood concentration of 169.17 mg/dL. In the group of PiMM NSCLC patients mean AAT serum concentration (206.33 mg/dL) was significantly higher than in the PiMM COPD group (171.39 mg/dL; P<0.0000). AAT concentration was significantly higher in squamous cell carcinoma (205.42 mg/dL) than adenocarcinoma (182.76 mg/dL; P<0.029) patients, and in advanced (IIIb-IV, 241.36 mg/dL) versus early stage disease (I-IIIa, 194.62 mg/dL, P<0.0000). IHC staining revealed strong AAT protein expression in FFPE tumor tissues from patients with lung adenocarcinoma and squamous cell carcinoma.
Conclusions
Our results might reflect an active AAT role in lung carcinogenesis as well as its local production by tumor cells. The positive association of AAT serum levels with stage and histology might be clinically valuable, if confirmed in a larger study. The study is on-going.
Keywords: Non-small cell lung cancer (NSCLC), tumor markers, alpha-1-antitrypsin (AAT)