UICC World Cancer Congress 2006

Objective: We have recently introduced a classification of NSCLC into the growth patterns, based on biologic behavior of whole tumor tissue in respect to normal lung tissue, with a significant prognostic value. The aim of this study is to validate the hypothesis that these growth patterns have a distinct biologic and prognostic profile. Methods: Hematoxylin-eosin stained tissue sections of 239 patients operated for NSCLC were classified into 3 growth patterns. One representative tissue section per patient was double immunostained with CD34 and KI67 antibodies. Endothelial cell proliferation fraction (ECPF), tumor cell proliferation fraction (TCPF), microvessel density (MVD) and Chalkley count were measured. A multiple Cox regression model was used to test the prognostic value of growth patterns for overall and disease-free survival. Results: According to our classification, 161 (67.4%) patients had a destructive (angiogenic), 33 (13.8%) a papillary (intermediate) and 48 (18.8%) an alveolar (nonangiogenic) growth pattern. There were significant differences in ECPF (p<0.001), TCPF (p<0.001), MVD (p<0.001) and Chalkley count (p<0.001) between the different growth patterns. Alveolar growth pattern had the lowest and destructive growth pattern had the highest ECPF. Multivariable analyses showed that growth pattern (p<0.001) and stage (p=0.001) were independent prognostic factors for overall and disease-free survival. These results indicate that growth patterns have a distinct biologic profile, implying that different growth patterns might respond differently to specific treatment modalities, such as anti-angiogenic therapy. Secondly, the proposed classification has an independent prognostic value providing a possible explanation for survival differences of patients in the same stage of disease.