Abstract
BackgroundMicrovessel density (MVD), as a derived marker for angiogenesis, has been associated with poor outcome in several types of cancer. This study aimed to evaluate the prognostic value of MVD in stage II and III colon cancer and its relation to tumour-stroma-percentage (TSP) and expression of HIF1A and VEGFA.MethodsFormalin-fixed paraffin-embedded (FFPE) colon cancer tissues were collected from 53 stage II and 54 (5-fluorouracil-treated) stage III patients. MVD was scored by digital morphometric analysis of CD31-stained whole tumour sections. TSP was scored using haematoxylin-eosin stained slides. Protein expression of HIF1A and VEGFA was determined by immunohistochemical evaluation of tissue microarrays.ResultsMedian MVD was higher in stage III compared to stage II colon cancers (11.1% versus 5.6% CD31-positive tissue area, p < 0.001). High MVD in stage II patients tended to be associated with poor disease free survival (DFS) in univariate analysis (p = 0.056). In contrast, high MVD in 5FU-treated stage III patients was associated with better DFS (p = 0.006). Prognostic value for MVD was observed in multivariate analyses for both cancer stages.ConclusionsMVD is an independent prognostic factor associated with poor DFS in stage II colon cancer patients, and with better DFS in stage III colon cancer patients treated with adjuvant chemotherapy.
Highlights
Microvessel density (MVD), as a derived marker for angiogenesis, has been associated with poor outcome in several types of cancer
Study design and population Based on a previously established well-documented retrospective cohort of 386 stage II and III colon cancer patients with no prior history of colorectal cancer (CRC) [34], we here selected a subset of stage II and stage III colon cancer patients of whom whole tissue sections were available for MVD analysis
This study addressed the analysis of microvessel density and its relation to disease stage and prognosis, in microsatellite stable stage II and III colon cancer patients
Summary
Microvessel density (MVD), as a derived marker for angiogenesis, has been associated with poor outcome in several types of cancer. The angiogenic pathway is often constitutively activated in tumours to meet their needs for nutrients and to facilitate tumour growth and metastasis. This is an early event in the development of cancer and can already be observed in pre-malignant lesions [1,2,3]. These newly formed blood vessels have a less distinct organized hierarchy [4], and are prone to vascular leakage for their irregular endothelial layer with. Tumours with high tumour-stroma percentage (TSP) are likely to express more angiogenic factors, leading to more angiogenesis, and angiogenesis-rich tumours may be associated with a worse prognosis
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