Prognostic value of a biologic classification of non-small-cell lung cancer into the growth patterns along with other clinical, pathological and immunohistochemical factors☆

Abstract

Classification of non-small-cell lung cancer (NSCLC) into growth patterns is based on the following question: What does the tumour do with normal lung parenchyma? There are only three possible ways according to which a tumour can behave: (1) preservation of lung tissue and use of its microenvironment for further growth, (2) destruction of lung tissue and formation of new microenvironment for continued expansion and (3) preservation of lung tissue and formation of new microenvironment (modulation). The aim of the current study is to test the prognostic value of growth-pattern classification along with other clinical, pathological and immunohistochemical factors. Clinicopathological factors of 239 patients operated for NSCLC were retrospectively reviewed. Preoperative smoking status was determined based on two prospectively independent questionnaires. Co-morbidity was determined based on Charlson co-morbidity index (CCI). Haematoxylin-eosin tissue sections were analysed for the determination of tumour growth patterns, histological types, grading, necrosis and desmoplasia. Tumour cell proliferation, endothelial cell proliferation and microvessel density were determined based on double immunostaining with CD34 and Ki67 antibodies. Follow-up data were updated in 2008. 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. Multiple Cox regression analysis showed that older age (p<0.001), lymph node metastasis (p<0.001), growth-pattern classification (p=0.036) and current smokers (p=0.027) were independent prognostic factors for overall survival. Similar results were obtained for disease-specific and disease-free survival. Papillary (hazard ratio=1.658 and confidence interval=1.001-2.748, p=0.050) and alveolar (hazard ratio=2.056 and confidence interval=1.305-3.237, p=0.002) growth patterns were independent predictors of early recurrence. Growth-pattern classification remains a significant prognostic factor in NSCLC providing a possible explanation for survival differences in the same disease stage.