Chromosome 9 instability and alterations of p16 gene in squamous cell carcinoma of the lung and in adjacent normal bronchi: FISH and immunohistochemical study.

Aims: p16, a tumour suppressor gene located at 9p21 chromosome and involved in cell cycle regulation, is often inactivated in lung carcinoma. Inactivation is also supported by the loss of p16 protein, a strong inhibitor of cyclin-dependent kinase (CDK) 4 and 6. The aim of this study was to examine alterations of p16 both in pulmonary squamous cell carcinoma (SCC) and in morphological normal bronchi contiguous with neoplasia. Methods and results: p16 gene and chromosome 9 alterations were examined by fluorescence in situ hybridization and the expression of p16 protein by immunohistochemistry in pulmonary surgical specimens from 31 patients with SCC. As controls, surgical specimens from 13 patients with non-neoplastic pathology were examined. Tumours showed molecular alterations for p16 gene and chromosome 9 abnormalities in, respectively, 29 ⁄ 31 and 19 ⁄ 31 cases respectively. p16 protein was unexpressed in 29 ⁄ 31 cases. In morphologically normal bronchi p16 gene and chromosome 9 alterations occurred in, respectively, 13 ⁄ 31 and 4 ⁄ 31 cases respectively; loss of protein immunoreactivity occurred in 14 ⁄ 31 cases. No alterations were seen in any of the control cases. Conclusions: Inactivation of p16 gene in histologically normal bronchi could aid the identification of individuals at risk of developing SCC of the lung.