title: Lymphatic vessel density as a prognostic marker in clinical stage I endocervical adenocarcinoma.
abstract: There are limited data evaluating the significance of lymphatic vessel density (LVD) as a prognostic marker in cervical adenocarcinoma. In this study, we investigated intratumoral and peritumoral LVD, using the lymphatic marker D2-40, as a prognostic marker in endocervical adenocarcinoma. Surgical specimens from 50 consecutive patients with endocervical adenocarcinoma treated with complete staging surgical procedures were reviewed. Selected tumor blocks were immunostained for D2-40 and CD31. Positively stained microvessels (MVs) were counted in densely vascular/lymphatic foci (hot spots) at 400x field in each specimen (0.17 mm). Results were expressed as the highest MV count identified within any single field. Both intratumoral CD31 MV and peritumoral D2-40 LVD showed significant correlation with depth of invasion (r=0.39, 0.37, respectively), percentage of circumferential involvement (r=0.36, 0.48, respectively), and lymphovascular invasion detected by D2-40 (r=0.45, 0.51, respectively; P<0.01). Only peritumoral D2-40 LVD showed a significant correlation with lymph node metastases (r=0.40; P<0.01), disease-free and overall survivals. Using univariate analysis, peritumoral D2-40 LVD showed significant correlation with lymphovascular invasion detected by D20-40 and lymph node metastases (P<0.05), which was maintained on multivariate analysis. D2-40 detected lymphovascular invasion in 16 of 50 (32%) cases, and showed a significant correlation with depth of invasion, lymph node metastases, involvement of parametrium (r=0.41, 0.38, 0.32, respectively; P<0.01), and disease-free survival. Our study showed that both angiogenesis and lymphangiogenesis play an important role in the progression of endocervical adenocarcinoma, and that peritumoral D2-40 LVD is an independent predictor of lymph node metastasis.
authors.affiliation: Department of Pathology, Sunnybrook Health Sciences Center/University of Toronto, Ontario Canada. reda.saad@sunnybrook.ca
authors.forename: Reda S
authors.initials: RS
authors.lastname: Saad
authors.forename: Nadia
authors.initials: N
authors.lastname: Ismiil
authors.forename: Zeina
authors.initials: Z
authors.lastname: Ghorab
authors.forename: Sharon
authors.initials: S
authors.lastname: Nofech-Mozes
authors.forename: Valérie
authors.initials: V
authors.lastname: Dubé
authors.forename: Allan
authors.initials: A
authors.lastname: Covens
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Khalifa
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000473:pathology*; D000328:Adult; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000098:blood supply / Q000473:pathology*; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C500987:monoclonal antibody D2-40