Genetics and Genomics

British Journal of Cancer (2008) 98, 1118–1124. doi:10.1038/sj.bjc.6604256 www.bjcancer.com
Published online 19 February 2008

High tumour islet macrophage infiltration correlates with improved patient survival but not with EGFR mutations, gene copy number or protein expression in resected non-small cell lung cancer

D-W Kim1,4, H S Min2, K-H Lee1, Y J Kim1,4, D-Y Oh1,4, Y K Jeon2, S-H Lee1,4, S-A Im1,4, D H Chung2,4, Y T Kim3, T-Y Kim1,4, Y-J Bang1,4, S W Sung3, J H Kim3 and D S Heo1,4

  1. 1Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
  2. 2Department of Pathology, Seoul National University Hospital, Seoul, Korea
  3. 3Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul, Korea
  4. 4Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

Correspondence: Professor DS Heo, Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongro-Gu, Seoul 110-744, Korea. E-mail: heo1013@snu.ac.kr

Received 26 July 2007; Revised 2 January 2008; Accepted 18 January 2008; Published online 19 February 2008.

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Abstract

The purpose of this study was to investigate the prognostic value of tumour-associated macrophages with a focus on micro-anatomical localisation and determine whether molecular changes of the epidermal growth factor receptor (EGFR) are related to macrophage infiltration in resected non-small cell lung cancer (NSCLC). One hundred and forty-four patients were included in this study. Immunohistochemistry was used to identify CD68+ macrophages in the tumour islet and surrounding stroma. Epidermal growth factor receptor mutations were studied by direct sequencing. The EGFR gene copy number and protein expression were analysed by fluorescence in situ hybridisation and immunohistochemistry. Patients with a high tumour islet macrophage density survived longer than did the patient with a low tumour islet macrophage density (5-year overall survival rate was 63.9 vs 38.9%, P=0.0002). A multivariate Cox proportional hazard analysis revealed that the tumour islet macrophage count was an independent prognostic factor for survival (hazard ratio 0.471, 95% confidence interval 0.300–0.740). However, EGFR mutations, gene copy number, and protein expression were not related to the macrophage infiltration. In conclusion, tumour islet macrophage infiltration was identified as a strong favourable independent prognostic marker for survival but not correlated with the molecular changes of the EGFR in patients with resected NSCLC.

Keywords:

macrophage, non-small cell lung cancer, epidermal growth factor receptor, survival analysis