Morphological features of lymphatic microvessel density depending on stage of cervical neoplasia

Abstract

Incomplete characterization of the uterine cervix cancer from molecular point of view represents the main problem for the use of a proper therapy in this disease. Few data are available about D2-40 expression in lymphatic endothelial cells and also in tumor cells from uterine cervix cancer. The aim of the present work was to study the involvement of lymphatics in tumor progression of the uterine cervix lesions. There were investigated targeted biopsies of the uterine cervix and specimens taken from conization in patients with macroscopically detectable lesions. We used D2-40 immunostaining to highlight lymphatic vessels from squamous cell metaplasia (n=17), cervical intraepithelial neoplasia (n=l 1), carcinoma in situ (n=3), microinvasive carcinoma (n=4) and invasive carcinoma (n=19) using Avidin-Biotin technique (LSAB+). Type and distribution of lymphatics in different lesions of the cervix were analyzed. Type and distribution of LVs(lymphatic vessels) in the normal uterine cervix. In the superficial lamina propria of the normal cervix, LVs were very rare and small or even absent. In all normal cases, LVs, if found, were located at some distance from the epithelium. In the deep lamina propria we noticed the presence of D2-40 positive vessels with density that ranged between 5 and 6.6 vessels/x200, with an average of 5.8. In the muscle layer, LMVD (lymphatic microvessel density) ranged between 5.3 and 7, with an average of 6.15. Type and distribution of LVs in precursor lesions. In squamous cell metaplasia the distribution and number of LVs was not significantly different from results found in the normal cervix. A significant increase in the number of LVs was found in cases with cervical intraepithelial neoplasia high-grade. In these cases, we noticed the presence of many LVs located close to the epithelium and was associated with a significantly increased expression of D2-40 in basal cells. LMVD in CIN ranged between 10.3 and 19.3 with an average of 14.8 vessels/x2005. Lymphatics in microinvasive and invasive carcinoma. Intratumoral LVs were found in both microinvasive and invasive carcinoma. Intratumoral LVs were very rare, small, with narrow lumen, irregular wall and without content of tumor cells. Peritumoral LVs were significantly more numerous, large, sinuous, and occasionally contained tumor cells. LMVD in cases with invasive carcinoma ranged from 0 to 12.3, with an average of 6.15. In microinvasive carcinoma, LMVD has values ranged between 3 and 11, with an average of 8.15. We found significant correlation between lymphatic microvessel density and tumor grade and particular distribution of the lymphatics linked to histopathologic type of the lesions. Our results showed differences in the distribution and D2-40 expression in lymphatic vessels and tumor cells from the cervix lesions linked to histopathology and tumor grade.