title: Presence of tumour high-endothelial venules is an independent positive prognostic factor and stratifies patients with advanced-stage oral squamous cell carcinoma.
abstract: Staging of oral squamous cell carcinoma is based on the tumour-node-metastasis (TNM) system, which has been deemed insufficient for prognostic purposes. Hence, better prognostic tools are needed to reflect the biological diversity of these cancers. Previously, high numbers of specialized blood vessels called high-endothelial venules have been reported to be associated with prolonged survival in patients with breast cancer. In this study, we analysed the prognostic value and morphological characteristics of tumour-associated high-endothelial venules in oral cancer. The presence of tumour-associated high-endothelial venules was evaluated by immunohistochemistry in 75 patients with oral squamous cell carcinoma and analysed with correlation to clinicopathological parameters, patients' survival and vessel morphology. Ten of the samples were analysed at multiple levels to evaluate intratumoural heterogeneity. The presence of tumour-associated high-endothelial venules was found to be associated with lower disease-specific death in multivariate regression analyses (P = 0.002). High-endothelial venules were present in all (n = 53) T1-T2 tumours, but only in two thirds (n = 14) of the T3-T4 tumours. The morphology of high-endothelial venules was heterogeneous and correlated with lymphocyte density. High-endothelial venules were found to be distributed homogeneously within the tumours. We found the presence of tumour-associated high-endothelial venules to be an easy-to-use, robust, and independent positive prognostic factor for patients with oral cancer. Absence of these vessels in advanced-stage tumours might identify patients with more aggressive disease. Evaluating the presence of tumour-associated high-endothelial venules might help to tailor the treatment of oral cancer patients to their individual needs.
authors.affiliation: Department of Medical Biology, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, 9037, Tromsø, Norway. anna.wirsing@uit.no.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Wirsing
authors.affiliation: Department of Medical Biology, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, 9037, Tromsø, Norway.|Department of Otorhinolaryngology, University Hospital of North Norway, 9038, Tromsø, Norway.
authors.forename: Oddveig G
authors.initials: OG
authors.lastname: Rikardsen
authors.affiliation: Department of Medical Biology, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, 9037, Tromsø, Norway.|Department of Clinical Pathology, University Hospital of North Norway, 9038, Tromsø, Norway.
authors.forename: Sonja E
authors.initials: SE
authors.lastname: Steigen
authors.affiliation: Department of Medical Biology, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, 9037, Tromsø, Norway.|Department of Clinical Pathology, University Hospital of North Norway, 9038, Tromsø, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Uhlin-Hansen
authors.affiliation: Department of Medical Biology, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, 9037, Tromsø, Norway.|Department of Clinical Pathology, University Hospital of North Norway, 9038, Tromsø, Norway.
authors.forename: Elin
authors.initials: E
authors.lastname: Hadler-Olsen
mesh_terms: D000293:Adolescent; D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000098:blood supply* / Q000473:pathology*; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis; D014699:Venules / Q000473:pathology*; D055815:Young Adult
keywords: High-endothelial venules; Inflammation; Lymphocyte trafficking; Oral squamous cell carcinoma; Peripheral node addressin; Prognostic factor