Fascin-1, the most expressed form of
fascin in vertebrate tissues, is an actin-bundling
protein that induces cell membrane protrusions and increases motility of normal and transformed epithelial cells. Very few data are available on the role of this
protein in
nonsmall cell lung cancer (NSCLC). Two hundred and twenty patients with stage I NSCLC and long-term follow-up were evaluated immunocytochemically for
fascin expression. Overall, variable
fascin immunoreactivity was detected in 98% of 116
squamous cell carcinomas, in 78% of 96
adenocarcinomas, in 83% of six
large cell carcinomas, and in the two
adenosquamous carcinomas under study. Neoplastic emboli were commonly decorated by the antifascin antibody (P<0.001), also when the surrounding invasive
carcinoma was unreactive.
Fascin immunoreactivity correlated with high tumour grade (P=0.017) and, in
adenocarcinomas, with high Ki-67 labelling index (P=0.021).
Adenocarcinomas with a prevalent bronchiolo-alveolar in situ component were less commonly immunoreactive for
fascin than invasive tumours (P=0.005). Contralateral thoracic or distant
metastases were associated significantly with diffuse (>60% immunoreactive tumour cells)
fascin expression in
adenocarcinomas (P=0.043), and marginally with strong
fascin immunostaining in
squamous cell carcinomas (P=0.13). No associations were noted with any other clinicopathological variables tested. Patients with tumours showing diffuse (>60% immunoreactive neoplastic cells) and/or strong immunoreactivity for
fascin had a shorter survival (P=0.006 for
adenocarcinomas and P=0.026 for
squamous cell carcinomas), even after multivariate analysis (P=0.014 and 0.050, respectively). The current study documents for the first time that
fascin is upregulated in invasive and more aggressive NSCLC, being an independent prognostic predictor of unfavourable
clinical course of the disease. Targetting the
fascin pathway could be a novel therapeutic strategy of NSCLC.