Fax: (617) 264-5118
Immunohistochemical markers associated with brain metastases in patients with nonsmall cell lung carcinoma†
Version of Record online: 20 AUG 2008
Copyright © 2008 American Cancer Society
Volume 113, Issue 8, pages 2129–2138, 15 October 2008
How to Cite
Saad, A. G., Yeap, B. Y., Thunnissen, F. B. J. M., Pinkus, G. S., Pinkus, J. L., Loda, M., Sugarbaker, D. J., Johnson, B. E. and Chirieac, L. R. (2008), Immunohistochemical markers associated with brain metastases in patients with nonsmall cell lung carcinoma. Cancer, 113: 2129–2138. doi: 10.1002/cncr.23826
Presented in part at the 2007 Annual Meeting of the United States and Canadian Academy of Pathology (Pulmonary Pathology Society Trainee Award), San Diego, California, March 24-30, 2007.
- Issue online: 3 OCT 2008
- Version of Record online: 20 AUG 2008
- Manuscript Accepted: 9 JUN 2008
- Manuscript Revised: 13 MAY 2008
- Manuscript Received: 21 MAR 2008
- The National Institutes of Health. Grant Numbers: CA90578, CA074386, CA092824
- International Mesothelioma Program
- epidermal growth factor receptor;
- Ki-67 labeling index;
- overall survival;
- tumor markers;
- vascular endothelial growth factor
To the authors' knowledge, there are no reliable markers able to identify patients with nonsmall cell lung cancer (NSCLC) that will develop metastases to the brain. The authors investigated associations between immunohistochemical markers and the development of brain metastases in patients with NSCLC.
This was a hospital-based, case-control study of patients who were newly diagnosed with NSCLC between 1989 and 2003, developed brain metastases, and had pathology material available from both the primary NSCLC and the brain metastases. These patients were compared with a control group of patients who had NSCLC and no evidence of brain metastases. NSCLC was examined for expression levels of Ki-67, caspase-3, vascular endothelial growth factor A (VEGF-A), VEGF-C, E-cadherin, and epidermal growth factor receptor (EGFR) in 54 surgical pathology specimens using immunohistochemistry, and associations were evaluated between those markers and the development of brain metastases.
Brain metastases developed after a median of 12.5 months (range, 1.7-89.4 months) after the diagnosis of NSCLC. A significantly increased risk of developing brain metastases was associated with patients with NSCLC who had primary tumors with high Ki-67 levels (adjusted odds ratio [OR] of 12.2; 95% confidence interval [95% CI], 2.4-70.4 [P < .001]), low caspase-3 expression (adjusted OR of 43; 95% CI, 5.3 to >100 [P < .001]), high VEGF-C expression (adjusted OR of 14.6; 95% CI, 2.0 to >100 [P < .001]), and low E-cadherin (adjusted OR of 3.6; 95% CI, 0.9-16.4 [P = .05]). No significant risk was associated with VEGF-A or EGFR expression. High Ki-67 expression also was associated with a shorter overall survival (P = .04).
The results of the current study indicated that patients with NSCLC who had high Ki-67 expression, low caspase-3 expression, high VEGF-C expression, and low E-cadherin expression in their tumors may benefit from close surveillance because they may have an increased risk of developing brain metastases. Cancer 2008. © 2008 American Cancer Society.