HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

GASC1 expression in lung carcinoma is associated with smoking and prognosis of squamous cell carcinoma

Katri Uimonen1,2, Heta Merikallio3, Paavo Pääkkö4, Terttu Harju3, Arto Mannermaa1,2, Jorma Palvimo5, Veli-Matti Kosma1,2 and Ylermi Soini1,2

1Institute of Clinical Medicine, Department of Clinical Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland, Cancer Center of Eastern Finland, 2Imaging Center, Department of Clinical pathology, Kuopio University Hospital, Kuopio, Finland, 3Institute of Clinical Medicine, Department of Internal Medicine, Respiratory Unit, Centre of Excellence in Research, University of Oulu, Oulu, Finland, 4Department of Pathology, Oulu University Hospital, Oulu, Finland and 5Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland, Cancer Center of Eastern Finland

Offprint requests to: Ylermi Soini, MD, PhD, Department of Pathology and Forensic Medicine, School of Medicine, Cancer Center of Eastern Finland, University of Eastern Finland, Po Box 1627, FI-70211 Kuopio, Finland. e-mail: ylermi.soini@uef.fi


Summary. GASC1 (gene amplified in squamous cell carcinoma 1) encodes a nuclear protein that epigenetically catalyses the lysine demethylation of histones. We investigated the expression of GASC1 in different histological subtypes of lung cancer (n=289). Percentage value of GASC1 immunohistochemical expression was evaluated separately in the nuclei and cytoplasms of epithelial cancer cells. The results were compared with clinicopathologic factors and the smoking history of the patients. In lung tumor cells, 38% of nuclei and 54% of the cytoplasms stained positive for GASC1. Adeno-carcinomas expressed more GASC1 nuclear (p=0.00011) and cytoplasmic (p=0.00074) positivity than squamous cell carcinoma. Smokers displayed less nuclear and cytoplasmic GASC1 expression than non-smokers (p=0.028 and p=0.036, respectively). Similarly, patients with more cytoplasmic positive staining had fewer pack years (p=0.043). Nuclear GASC1 expression had an impairing effect on survival when all histological lung cancer types were analysed together (p=0.039) and separately in squamous cell lung carcinoma (p=0.016). The results reveal that GASC1 expression is higher in adenocarcinoma than squamous cell carcinoma. Smoking decreases GASC1 expression in tumor cells, indicating that tobacco smoke may influence the methylation of histone 3 lysine residues in lung cancer. Nonetheless, nuclear GASC1 predicts a poor prognosis, especially in squamous cell carcinoma. Histol Histopathol 29, 797-804 (2014)

Key words: GASC1, Epigenetics, Histone demethylase, Lung cancer

DOI: 10.14670/HH-29.797