Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disorder with a poor prognosis. Epithelial instability is a crucial step in the development and progression of the disease including neoplastic transformation. Few tissue markers regarding epithelial instability have been reported in IPF. Squamous cell carcinoma antigen (SCCA) is a serine protease inhibitor typically expressed by dysplastic and neoplastic cells of epithelial origin, more often in squamous cell tumours. At present no information is available on its expression in IPF.
Methods: SCCA and transforming growth factor-β (TGF-β) expression in surgical lung biopsies from 22 IPF patients and 20 control cases. An in vitro study using A549 pneumocytes was also conducted to investigate the relationship between SCCA and TGF-β expression. SCCA and TGF-β epithelial expression were evaluated by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). SCCA values were correlated with different pathological and clinical parameters. Time course analysis of TGF-β expression in A549 pneumocytes incubated with different SCCA concentrations was assessed by real time RT-PCR.
Results: SCCA was expressed in many metaplastic alveolar epithelial cells in all IPF cases with a mean value of 24.9% while it was seen in only two control patients in up to 5% of metaplastic cells. In IPF patients SCCA correlated positively with the extension of fibroblastic foci (r = 0.49, p = 0.02), the expression of TGF-β(r = 0.78, p < 0.0001) and with DLCO decline at 9 months of follow-up (r = 0.59, p = 0.01). In vitro experiments showed that incubation of cultured cells with SCCA induced TGF-βexpression, with a peak at 24 hours.
Conclusion: Our findings provide for the first time a potential mechanism by which SCCA secreted from metaplastic epithelial cells may exert a profibrotic effect in IPF. SCCA could be an important biomarker in this incurable disease.