title: Improved computer-assisted analysis of the global lymphatic network in human cervical tissues.
abstract: Lymphatic dissemination is a key event in cervical cancer progression and related tumor lymphatic markers are viewed as promising prognostic factor of nodal extension. However, validating such parameters requires an objective characterization of the lymphatic vasculature. Here, we performed a global analysis of the lymphatic network using a new computerized method applied on whole uterine cervical digital images. Sixty-eight cases of cervical neoplasia (12 CIN3, 10 FIGO stage 1A and 46 stage IB1) and 10 cases of normal cervical tissue were reacted with antibodies raised against D2-40, D2-40/p16 and D2-40/Ki67. Immunostained structures were automatically detected on whole slides. The lymphatic vessel density (D2-40), proliferating lymphatic vessel density (D2-40/ki67) and spatial lymphatic distribution in respect to the adjacent epithelium were assessed from normal cervix to early cervical cancer and correlated with lymphovascular space invasion and lymph node status. Prominent lymphatic vessel density and proliferating lymphatic vessel density are detected under the transformation zone of benign cervix and no further increase is noted during cancer progression. Notably, a shift of lymphatic vessel distribution toward the neoplastic edges is detected. In IB1 cervical cancer, although intra- and peritumoral lymphatic vessel density are neither correlated with lymphovascular space invasion nor with lymph node metastasis, a specific spatial distribution with more lymphatic vessels in the vicinity of tumor edges is predictive of lymphatic dissemination. Herein, we provide a new computerized method suitable for an innovative detailed analysis of the lymphatic network. We show that the transformation zone of the benign cervix acts as a baseline lymphangiogenic niche before the initiation of neoplastic process. During cancer progression, this specific microenvironment is maintained with lymphatic vessels even in closer vicinity to tumor cells.
authors.affiliation: Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Cancer), University of Liège, Pathology Tower (B23), Liège, Belgium.
authors.forename: Cédric
authors.initials: C
authors.lastname: Balsat
authors.affiliation: Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Cancer), University of Liège, Pathology Tower (B23), Liège, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Signolle
authors.affiliation: Department of Obstetrics and Gynecology, Hospital of la Citadelle, Liège, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Goffin
authors.affiliation: Department of Pathology, Hospital of la Citadelle, Liège, Belgium.
authors.forename: Katty
authors.initials: K
authors.lastname: Delbecque
authors.affiliation: GRECAN, University of Caen, François Baclesse Comprehensive Cancer Center, Caen, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Plancoulaine
authors.affiliation: Departement of Gynecologic Oncology, CHU of Montréal, Montréal, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Sauthier
authors.affiliation: Departement of Gynecologic Oncology, CHU of Montréal, Montréal, Canada.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Samouëlian
authors.affiliation: Department of Obstetrics and Gynecology, Hospital of la Citadelle, Liège, Belgium.
authors.forename: Aude
authors.initials: A
authors.lastname: Béliard
authors.affiliation: Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Cancer), University of Liège, Pathology Tower (B23), Liège, Belgium.
authors.forename: Carine
authors.initials: C
authors.lastname: Munaut
authors.affiliation: Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Cancer), University of Liège, Pathology Tower (B23), Liège, Belgium.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.affiliation: Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Cancer), University of Liège, Pathology Tower (B23), Liège, Belgium.
authors.forename: Silvia
authors.initials: S
authors.lastname: Blacher
authors.affiliation: Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Cancer), University of Liège, Pathology Tower (B23), Liège, Belgium.
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.affiliation: Department of Obstetrics and Gynecology, CHU of Liège, Liège, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Kridelka
mesh_terms: D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007150:Immunohistochemistry; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis / Q000473:pathology*; D042601:Lymphatic Vessels / Q000473:pathology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000473:pathology*