Tumor angiogenesis correlates with histologic type and metastasis in non-small-cell lung cancer

This study investigated the clinico-pathologic correlation of tumor angiogenesis in non-small-cell lung cancers. Formalin-fixed, paraffin-embedded surgical specimens of 55 consecutive patients with primary non-small-cell lung cancers were examined. Included were 26 squamous cell carcinomas and 29 adenocarcinomas. Twenty-five patients had stage I disease, eight patients had stage II disease, and 22 patients had stage IIIA or IIIB disease. Among them, 28 had nodal metastasis and 27 did not. The microvessel was demonstrated by immunocytochemical staining for factor VIII and platelet endothelial cell adhesion molecules (PECAM-1). The microvessels in the areas of highest neovascularization were counted under light microscopy in 200× field by two independent observers without knowledge of clinical information. At least three separate fields were counted for each specimen. The Mann-Whitney U test was used for statistical analysis. The microvessel counts in adenocarcinoma were significantly higher than in the squamous cell carcinoma (54.4 ± 35.65 versus 26.16 ± 20.46 in factor VIII staining and 80.52 ± 48.42 versus 40.04 ± 32.33 in PECAM-1 staining; p < 0.001). The microvessel counts in patients with Stages I-II disease were significantly lower than that of stages IIIA-IIIB disease (23.63 ± 16.21 versus 65.36 ± 31.92 in factor VIII staining and 41.85 ± 36.76 versus 93.00 ± 43.08 in PECAM-1; p < 0.001). Patients with nodal metastasis had higher microvessel density than those without nodal metastasis (56.67 ± 35.55 versus 23.44 ± 15.77 in factor VIII staining and 86.89 ± 46.46 versus 36.30 ± 25.83 in PECAM-1 staining; p < 0.001). The microvessel counts in patients with early postoperative metastasis were higher than those without early metastasis (64.47 ± 34.60 versus 27.53 ± 20.48 in factor VIII staining and 96.79 ± 48.14 versus 44.39 ± 38.0 in PECAM-1 staining; p < 0.001). Our results suggest that microvessel density correlates with histologic types, stages of disease, nodal status, and postoperative metastasis in non-small-cell lung cancer. The high microvessel counts in adenocarcinoma may contribute to the higher metastatic potential compared with squamous cell carcinoma.