Originally published as JCO Early Release 10.1200/JCO.2005.01.4910 on October 11 2005

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Macrophage and Mast-Cell Invasion of Tumor Cell Islets Confers a Marked Survival Advantage in Non–Small-Cell Lung Cancer

Tomas J. Welsh, Ruth H. Green, Donna Richardson, David A. Waller, Kenneth J. O'Byrne, Peter Bradding

From the Department of Infection, Immunity, and Inflammation; Department of Cancer Studies and Molecular Medicine, University of Leicester Medical School; Department of Cardiothoracic Services, University Hospitals of Leicester National Health Service Trust, Glenfield Hospital, Leicester; Thoracic Oncology Research Group, St James's Hospital and Trinity College, Dublin, Ireland

Address reprint requests to Peter Bradding, MD, Department of Respiratory Medicine, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom; e-mail: pbradding{at}hotmail.com.

PURPOSE: The role played by the innate immune system in determining survival from non–small-cell lung cancer (NSCLC) is unclear. The aim of this study was to investigate the prognostic significance of macrophage and mast-cell infiltration in NSCLC.

METHODS: We used immunohistochemistry to identify tryptase⁺ mast cells and CD68⁺ macrophages in the tumor stroma and tumor islets in 175 patients with surgically resected NSCLC.

RESULTS: Macrophages were detected in both the tumor stroma and islets in all patients. Mast cells were detected in the stroma and islets in 99.4% and 68.5% of patients, respectively. Using multivariate Cox proportional hazards analysis, increasing tumor islet macrophage density (P < .001) and tumor islet/stromal macrophage ratio (P < .001) emerged as favorable independent prognostic indicators. In contrast, increasing stromal macrophage density was an independent predictor of reduced survival (P = .001). The presence of tumor islet mast cells (P = .018) and increasing islet/stromal mast-cell ratio (P = .032) were also favorable independent prognostic indicators. Macrophage islet density showed the strongest effect: 5-year survival was 52.9% in patients with an islet macrophage density greater than the median versus 7.7% when less than the median (P < .0001). In the same groups, respectively, median survival was 2,244 versus 334 days (P < .0001). Patients with a high islet macrophage density but incomplete resection survived markedly longer than patients with a low islet macrophage density but complete resection.

CONCLUSION: The tumor islet CD68⁺ macrophage density is a powerful independent predictor of survival from surgically resected NSCLC. The biologic explanation for this and its implications for the use of adjunctive treatment requires further study.

Presented in part as an abstract at the British Thoracic Society Winter Meeting, London, United Kingdom, December 1-4, 2004, and at the American Thoracic Society Annual International Conference, San Diego, CA, May 20-25, 2005.

Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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