Expression of fibroblast activation protein in dogs with idiopathic pulmonary fibrosis or lung cancer

Canine Idiopathic Pulmonary Fibrosis (CIPF) is a progressive fibrotic interstitial lung disease affecting predominantly the old West Highland White Terrier (WHWT). Fibroblast activation protein (FAP) is a cell surface protease specifically expressed in areas of active tissue remodelling and upregulated in various types of cancers. The aim of this study was to assess the expression and localization of FAP in the lungs of WHWTs affected with CIPF and in canine lung tumours, in comparison with healthy lungs. FAP expression was investigated by immunohistochemistry on lung biopsies from 22 WHWTs with CIPF, 8 dogs with lung cancer (6 adenocarcinomas, 1 histiocytic sarcoma, and 1 metastasized mammary carcinoma) and 15 old dogs (including 4 WHWTs) without lung disease. A staining index (absent, low, intermediate or high) was attributed according to the percentage of positive cells combined with the staining intensity. FAP was identified in the lungs from 20 WHWTs with CIPF (staining index high, intermediate, or low in respectively 11, 6 and 3 dogs), in 7 lung tumours (high and intermediate in respectively 6 and 1 dogs) but in 2 control WHWTs only (1 of each intermediate and low). FAP was expressed by fibroblasts in areas of active fibrosis in CIPF and by cancer-associated fibroblasts (all types of cancer) and cancer cells (5 adenocarcinomas only) in lung tumours. We hypothesize that positive results in 2 predisposed dogs may represent a very early-stage disease. FAP overexpression in lungs from dogs with CIPF and lung neoplasia opens new perspectives in the fields of diagnosis and therapy for both diseases, since FAP could be investigated as a biomarker or a therapeutic target.