title: A study into methodology and application of quantification of tumour vasculature in rectal cancer.
abstract: The application of new surgical techniques in combination with preoperative radiotherapy has minimised the risk of local recurrence in rectal cancer. However, distant metastasis is still a serious problem after seemingly curative resection in patients with rectal cancer. The present study aimed to evaluate the methodology for quantification and the characteristics of the tumour vasculature in relation to the development of metastasis in patients with rectal cancer. From a large multicentre trial, 88 patients were selected, ensuring a relatively high percentage of metastasis. This selection facilitates the study of tumour vasculature characteristics in relation to metastasis. Vessel number, perimeter and area were assessed at both the invasive front and intratumoural area. Hot-spot and random selections were performed simultaneously. The median of each vessel parameter in the study population was used to separate patients into a low- and high-vessel group. Differences in development of distant metastasis were studied between low- and high-vessel groups. The data of the present study show that only vascular perimeter randomly assessed at the invasive front was associated with distant metastasis. Patients with a high score had a lower distant metastasis rate than patients with a low score (37% and 62%, respectively). High-vessel perimeter was independent of tumor node metastasis staging, but was associated with an increased presence of immune cells, comprising T cells, mast cells, eosinophils and neutrophils. This methodological study on the biological relevance of various vessel characteristics showed that a large vascular endothelial surface, as reflected by a high perimeter, was the only vessel characteristic indicative of improved patient outcome. The underlying principle for this association may be the improved immune response.
authors.affiliation: Department of Pathology, UMC Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: Vlems
authors.forename: Erik
authors.initials: E
authors.lastname: van der Worp
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Laak
authors.forename: Cornelis
authors.initials: C
authors.lastname: van de Velde
authors.forename: Iris
authors.initials: I
authors.lastname: Nagtegaal
authors.forename: Han
authors.initials: H
authors.lastname: van Krieken
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009389:Neovascularization, Pathologic; D012004:Rectal Neoplasms / Q000098:blood supply* / Q000276:immunology / Q000473:pathology*; D016019:Survival Analysis