Detection of early lymphangiogenesis by lymphatic microvascular density and endothelial proliferation status in preneoplastic and neoplastic lesions of the uterine cervix

The characteristics of lymphangiogenesis in preneoplastic and neoplastic lesions of the uterine cervix are not well known and the role of this process in tumor progression and metastasis is not well understood. The aim of the present study was to characterize the morphology and distribution of lymphatic vessels and lymphatic proliferative status and to evaluate the value of lymphatic microvascular density (LMVD) in premalignant and malignant lesions of the uterine cervix. One hundred and twenty-eight paraffin-embedded cervical specimens were immunostained with D2-40 antibody specific for lymphatic endothelial cells. Colocalization of D2-40 and Ki67 for the proliferative characterization of lymphatic vessels was obtained by performing double immunostaining. A low density of lymphatic vessels was detected in normal cervix and squamous metaplasia. Intense and particular lymphangiogenic response was found in low and high grade squamous intraepithelial lesions and microinvasive carcinoma. Lymphatic proliferation occurred early in cervical lesions, being more active in premalignant lesions and microinvasive carcinomas than in invasive lesions. Our results suggest an early initiation of an active lymphangiogenesis in cervical lesions. These findings support the hypothesis that cervical preneoplastic lesions represent a critical point in the development of the lymphatic network vasculature. Early lymphangiogenesis could explain lymph node metastasis associated with cervical invasive carcinomas at preliminary diagnosis.