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.