Original Article DOI: 10.1111/vco.12002 EGFR overexpression in canine primary lung cancer: pathogenetic implications and impact on survival † S. Sabattini 1 , F. R. Mancini 1 , L. Marconato 2 , B. Bacci 2 , F. Rossi 2 , M. Vignoli 2 and G. Bettini 1 1 Department of Veterinary Medical Sciences, Alma Mater Studiorum - University of Bologna, Ozzano Dell’Emilia, Bologna, Italy 2 Veterinary Clinic dell’Orologio/Veterinary Oncologic Center, Sasso Marconi, Bologna, Italy Abstract This study reports the main clinicopathological features of primary lung cancer (PLC) in 37 dogs, with special regard to the pathogenetic and prognostic role of epidermal growth factor receptor (EGFR) overexpression. For each case the following characteristics were evaluated: tumour-node-metastasis (TNM) stage, tumour histotype, histological grade, mitotic activity and immunohistochemical expression of EGFR. In samples with available normal lung tissue, the amount of background anthracosis was also measured by image analysis. In 27 tumours (73%) a variable number of cells (20 – 100%) stained positively for EGFR. The proportion of EGFR-positive tumours was significantly higher in cases with background anthracosis, and the amount of anthracosis was correlated with the percentage of positive tumour cells. Additionally, a trend towards shortened survival for the high EGFR group was observed. These findings suggest an involvement of EGFR signalling pathway in canine PLC, a negative prognostic significance of protein overexpression and its potential implication in air pollution carcinogenesis. Keywords dog, EGFR, lung cancer, pollution, prognosis, tyrosine kinase Introduction The epidermal growth factor receptor (EGFR) belongs to the receptor tyrosine kinase (RTK) family, a group of transmembrane proteins involved in cell-to-cell signal transduction. EGFR deregulations are regarded as a potential initiating event in human lung carcinogenesis, although their exact role still needs to be elucidated. 1 – 3 In humans, EGFR expression increases along with the severity of pulmonary dysplastic epithelial lesions, and is detected in up to 80% of non-small cell lung carcinomas (hNSCLCs); 4,5 notably, EGFR mutations are largely limited to never smokers or light smokers. 6 EGFR overexpression † Presented at the 2011 ESVONC Annual Congress, Glasgow, United Kingdom, March 25, 2011. is hypothesized to confer a proliferative advantage to neoplastic cells, potentially stimulating tumour development and progression. For these reasons, molecularly targeted agents directed against EGFR are regarded as a key treatment in hNSCLCs. 7 Primary lung cancer (PLC) is much more uncommon in dogs than in humans, accounting for approximately 1% of all canine tumours, 8 but its occurrence is increasingly reported. This trend is not only partially attributable to improved diagnostic procedures, greater availability of necropsy records and increased pet longevity, but also possibly to environmental changes. Several studies have raised the question as to whether human factors, such as passive cigarette smoking and/or urban living, may enhance the risk of lung tumours in dogs. 9 – 12 A higher incidence of Correspondence address: Prof. Giuliano Bettini Department of Veterinary Medical Sciences University of Bologna Via Tolara di Sopra, 50 40064 Ozzano Dell’Emilia (BO), Italy e-mail: giuliano.bettini@unibo.it © 2012 Blackwell Publishing Ltd 1