Neovascularization in hyperplastic, metaplastic and potentially preneoplastic lesions of the bronchial mucosa

Abstract

Angiogenesis is important in a large number of normal and pathological processes including tumour growth and development, inflammation and in wound healing. We investigated whether neovascularization exists in hyperplastic, metaplastic and potentially preneoplastic lesions of the bronchial mucosa as prestages for lung cancer. Biopsy specimens from 86 patients were investigated light microscopically. Formalin-fixed and paraffin-embedded specimens of regular bronchial mucosa including epithelium, basement membrane zone and tunica propria (n = 12) without inflammation were compared with specimens with inflammatory reaction (n = 9), basal cell- and goblet cell hyperplasia (n = 24), squamous cell metaplasia (n = 9), squamous cell metaplasia with different degrees of dysplasia (n = 11), specimens of micropapillomatosis (n = 9) and 13 cases with carcinoma in situ. The grade of neovascularization was assessed by the microvessel density, which was obtained by an immunohistochemical staining of endothelial cells using factor VIII-related antigen and determined by an automatic image-analysing-system. Microvessels were counted in selected areas of highest neovascularization on a x 100 field 0.4 mm underneath the basement membrane zone in the tunica propria. Microvessel count, minimal and maximal diameter of the vessels were chosen as morphological variables. A significantly increased microvessel count with 33 vessels/0.6 mm2 was found in specimens with inflammation of the tunica mucosa (regular bronchial mucosa: 20 vessels/0.6 mm2). Microvessel diameter (surface of cut section) increased in specimens of bronchial mucosa with inflammation to 11.3 x 10(-4) mm2 (regular bronchial mucosa: 9.04 x 10(-4) mm2). Microvessel count increased in cases of squamous cell metaplasia (33 vessels/0.6 mm2) squamous cell metaplasia with different degrees of dysplasia (50 vessels/0.6 mm2) and carcinoma in situ with 61 vessels/0.6 mm2. With increasing dysplasia, increasing neo-vascularization was found in close vicinity to the basement membrane zone. Simultaneously, interepithelial sprouts of endothelial cells were seen. Qualitative and quantitative differences were thus found in potentially preneoplastic lesions.