Prognostic value of nonangiogenic and angiogenic growth patterns in non-small-cell lung cancer

Abstract

An essential prerequisite of nonangiogenic growth appears to be the ability of the tumour to preserve the parenchymal structures of the host tissue. This morphological feature is visible on a routine tissue section. Based on this feature, we classified haematoxylin and eosin-stained tissue sections from 279 patients with non-small-cell lung cancer into three growth patterns: destructive (angiogenic; n=196), papillary (intermediate; n=38) and alveolar (nonangiogenic; n=45). A Cox multiple regression model was used to test the prognostic value of growth patterns together with other relevant clinicopathological factors. For overall survival, growth pattern (P=0.007), N-status (P=0.001), age (P=0.020) and type of operation (P=0.056) were independent prognostic factors. For disease-free survival, only growth pattern (P=0.007) and N-status (P<0.001) had an independent prognostic value. Alveolar (hazard ratio=1.825, 95% confidence interval=1.117-2.980, P=0.016) and papillary (hazard ratio=1.977, 95% confidence interval=1.169-3.345, P=0.011) growth patterns were independent predictors of poor prognosis. The proposed classification has an independent prognostic value for overall survival as well as for disease-free survival, providing a possible explanation for survival differences of patients in the same disease stage.

Figure 1

Classification of non-small-cell lung cancer.

Figure 2

Growth patterns of non-small cell lung cancer are visible on routine H&E-stained tissue sections. (A) Destructive growth pattern (angiogenic): parenchymal structures of the lung are not preserved, but replaced by carcinoma cells and tumour-associated stroma. (B) Papillary growth pattern (intermediate): the lung parenchyma is preserved with formation of fibrovascular stalks originating from the alveolar septa. (C) Alveolar growth pattern (nonangiogenic): the tumour cell nests fill the alveolar spaces with preservation of alveolar septa and without formation of a tumour-associated stroma.

Figure 3

Disease-free survival according to growth pattern for patients in stage I (destructive vs papillary growth, P=0.0455 and destructive vs alveolar growth pattern, P=0.0465).