4.5 Article

Prognostic significance of gelsolin expression level and variability in non-small cell lung cancer

Journal

LUNG CANCER
Volume 46, Issue 1, Pages 29-42

Publisher

ELSEVIER SCI IRELAND LTD
DOI: 10.1016/j.lungcan.2004.03.022

Keywords

non-small cell lung cancer; gelsolin; variability; prognosis; survival; immunohistochemistry

Funding

  1. NCI NIH HHS [CA 72768, CA 016056] Funding Source: Medline

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Background: Gelsolin is an actin-binding protein that mediates cellular motility and maintains the integrity of cytosketetal structure. Diminished expression of gelsotin has been observed in human cancer cell lines and tumors. Studies of the prognostic effect of gelsolin expression (GE) in non-small cell lung cancer (NSCLC) are rare and results are inconsistent to date. The present study used immunohistochemistry to evaluate the prognostic effect of gelsolin expression in 155 patients with resectable NSCLC. Methods: Detection of gelsolin in tumor cells was performed by immunohistochemistry, and two approaches to classification were used to describe expression: expression level (negative, reduced or high) and expression uniformity (uniform or variable). Expression level was determined by a weighted index of intensity of staining (i.e., overall tendency) in the specimen. Expression uniformity was based on the presence or absence of variability in immunostaining within the tumor section. Chi-square test, student t-test, Cox proportional hazards regression and Kaplan-Meier survival analysis were used in data analyses. Results: After controlling for covariates, high Level gelsolin expression was significantly associated with poor survival compared with negative gelsolin expression in NSCLC, and this adverse prognostic effect was specific to patients with stage II tumors and for patients with squamous cell carcinomas. Similarly, variable gelsolin expression was significantly associated with poor survival compared with uniform gelsolin expression and this adverse prognostic effect was also specific to patients with stage II tumors and for patients with squamous cell carcinomas. Conclusion: High level gelsolin expression and variable gelsolin expression are adverse prognostic factors for NSCLC in this study, which might manifest the high motility and heterogeneity of tumor cells, two distinguishing characteristics for tumors with potentially enhanced invasive and dissemination capabilities. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

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