EGFR expression and air pollution carcinogenesis in canine primary lung tumours

Activating EGFR mutations are among possible initiating events in lung carcinogenesis. 40-80% of human NSCLC overexpress EGFR, and in preneoplastic lesions expression increases with the severity of dysplasia, likely indicating tumour development. Incidence of canine primary lung tumours (cPLT) is increasingly reported. A causative role of passive cigarette smoking and/or urban living was suggested. In a previous study we demonstrated a relationship between cPLT and pulmonary accumulation of particulate pollutants (anthracosis). However, the molecular pathways involved in cPLT carcinogenesis have never been characterized. This study investigates EGFR expression in cPLT and its potential association with anthracosis. Dogs diagnosed with PLT were retrospectively included. Primary pulmonary occurrence was confirmed by clinical and/or necropsy findings and TTF-1 expression. Tumour histological type, grade, proliferation activity and TNM stage were assessed, and available clinicopathological data were recorded. EGFR immunohistochemical expression was quali/quantitatively evaluated. In samples with available normal lung parenchyma, the amount of background anthracosis was measured by image-analysis. Thirty-seven cases of cPLT were included. In 27/37 cases (73%), a variable number of cells (range=11-100/mean=61%) stained positive for EGFR, independently from clinicopathological parameters. Background anthracosis was detected in 18/21 cases (86%). All EGFR-positive tumours developed in anthracotic lungs (P=0.006) and the percentage of EGFR-positive cells was proportional to the amount of anthracosis (P=0.0015). In 60% of positive tumours, EGFR was also detected in background lung anthracosis-associated dysplastic/hyperplastic lesions. The observed relationship between anthracosis and EGFR expression in cPLT and dysplastic epithelial lesions suggests the implication of EGFR signaling pathway in air pollution carcinogenesis.