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Open Access Highly Accessed Research article

Expression of Bim, Noxa, and Puma in non-small cell lung cancer

Jun Sakakibara-Konishi1*, Satoshi Oizumi1, Junko Kikuchi1, Eiki Kikuchi1, Hidenori Mizugaki1, Ichiro Kinoshita2, Hirotoshi Dosaka-Akita2 and Masaharu Nishimura1

Author Affiliations

1 First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan

2 Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

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BMC Cancer 2012, 12:286  doi:10.1186/1471-2407-12-286

Published: 12 July 2012

Abstract

Background

The BH3-only members of the Bcl-2 protein family have been proposed to play a key role in the control of apoptosis and in the initiation of the apoptotic pathways. In this study, we evaluated the expression of Bim, Noxa, and Puma in non-small cell lung cancer (NSCLC).

Methods

A total of 135 surgically resected NSCLCs were immunohistochemically assessed for Bim, Noxa, and Puma expression. The immunoscores were determined, and then its correlation with either the clinicopathological variables or the survival outcomes were analyzed.

Results

Immunohistochemical reactivity for Bim, Noxa, and Puma was detected in the cytoplasm of the tumor cells. Bim expression was associated with several clinicopathological factors, including sex (p < 0.001), smoking habit (p = 0.03), pathological histology (p = 0.001), pathological T stage (p = 0.03), pathological disease stage (p = 0.02), and differentiation of tumor (p < 0.001). Multivariate logistic regression analysis showed a significant correlation between low Bim expression and squamous cell carcinoma (p = 0.04), in addition to a correlation between high Bim expression and well differentiated tumors (p = 0.02). Analysis of cellular biological expression demonstrated a link between low Bim expression and high Ki67. While Noxa expression was also shown to be correlated with both smoking habit (p = 0.02) and the pathological histology (p = 0.03), there was no strong association observed between the expression and the clinical features when they were examined by a multivariate logistic regression analysis. No correlations were noted between Puma expression and any of the variables. Our analyses also indicated that the expression levels of the BH3-only proteins were not pertinent to the survival outcome.

Conclusions

The current analyses demonstrated that Bim expression in the NSCLCs was associated with both squamous cell carcinoma histology and tumor proliferation.