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Original Articles: General Thoracic

Different Growth Patterns of Non-Small Cell Lung Cancer Represent Distinct Biologic Subtypes

^a Department of Thoracic and Vascular Surgery, University Hospital Antwerp, Antwerp, Belgium
^b Department of Pathology, University Hospital Antwerp, Antwerp, Belgium
^c Department of Epidemiology and Social Medicine, University Hospital Antwerp, Antwerp, Belgium
^d Cancer Research Tumor Pathology Group, John Radcliffe Hospital, Oxford, United Kingdom

Accepted for publication August 23, 2007.

^_* Address correspondence to Dr Sardari Nia, Department of Thoracic and Vascular Surgery, University Hospital Antwerp, Wilrijkstraat 10, Antwerp, Edegem B2650, Belgium (Email: peymansardarinia{at}yahoo.com).

Background: We have recently shown the prognostic value of growth pattern classification in non-small cell lung cancer. The aim of this study is to validate the hypothesis that these growth patterns have a distinct angiogenic and proliferative profile.

Methods: Hematoxylin-eosin stained tissue sections of 239 patients with non-small cell lung cancer were classified into growth patterns. One representative tissue section per patient was double immunostained with CD34 and Ki-67 antibodies. Endothelial cell proliferation fraction, tumor cell proliferation fraction, microvessel density, and Chalkley count were assessed at the invading front and the center of the selected tumor section.

Results: According to the growth pattern classification, 161 patients (67.4%) had a destructive, 33 (13.8%) a papillary, and 45 (18.8%) an alveolar growth pattern. There were significant differences in endothelial cell proliferation fraction (p < 0.001), tumor cell proliferation fraction (p < 0.001), microvessel density (p < 0.001), and Chalkley count (p < 0.001) between the growth patterns. Multiple Cox regression analysis showed that a low endothelial cell proliferation fraction was consistently an independent prognostic factor for overall poor (hazard ratio = 0.93; confidence interval: 0.88 to 0.97, p = 0.002) and disease-free survival (hazard ratio = 0.94; confidence interval: 0.89 to 0.98, p = 0.007).

Conclusions: Growth patterns have a distinct angiogenic and proliferative profile. In non-small cell lung cancer, a low degree of angiogenesis (a low endothelial cell proliferation fraction) is associated with poor prognosis.