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J. Chorostowska-Wynimko
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-079 - The Serum Levels of Alpha-1 Antitrypsin Are Strongly Associated with Its Local Production by Tumor Cells in NSCLC Patients (ID 5438)
14:30 - 14:30 | Author(s): J. Chorostowska-Wynimko
- Abstract
Background:
Lung cancer and chronic obstructive pulmonary disease (COPD) share a common etiology. Despite the known associations of alpha-1 antitrypsin (AAT) deficiency with COPD and COPD with lung cancer, few studies examined the association of AAT and lung cancer. We have investigated AAT serum levels in PiMM non-small cell lung cancer (NSCLC) patients with respect to PiMM controls with COPD and benign lung nodules since AAT is an acute-phase protein. The AAT tumor tissue expression was analyzed in NSCLC group to evaluate the potential contribution of cancer cells in AAT production.
Methods:
Serum and matched FFPE tissue samples were collected from 194 NSCLC patients (stages I-IV) with PiMM phenotype of AAT. The serum concentrations of AAT and CRP were measured by nephelometry. The AAT protein expression in NSCLC tumor cells was assessed by immunohistochemistry. Reference groups consisted of 183 PiMM COPD and 50 PiMM patients with benign lung nodules (hamartoma, tuberculoma, granuloma and other).
Results:
In NSCLC patients mean AAT serum concentration (195.5 mg/dl) was significantly higher than in COPD group (171 mg/dl) and patients with benign lung nodules (154 mg/dl; p<0.0001). AAT concentration was significantly higher in SQC type (202 mg/dl) than ADC (175 mg/dl; p<0.029) patients, and in advanced (IIIb-IV, 247 mg/dl) versus early stage disease (I-IIIa, 190 mg/dl, p<0.0001). AAT levels significantly correlated with CRP (R=0.6; p<0.0001), however CRP level did not differentiate NSCLC from COPD. Importantly, the strong AAT expression observed in tumor tissue was positively associated with the higher AAT blood levels, while weak or no AAT expression directly correlated with the lower AAT blood levels (p<0.0079).
Conclusion:
We have demonstrated for the first time that the local production of AAT by tumor cells significantly contributes to the high levels of AAT in blood of NSCLC patients. The significant association of serum AAT levels with stage and histology of NSCLC may implicate clinical use of AAT as a biomarker or therapeutic target.
