Prospective study of intratumoral microvessel density, p53 expression and survival in colorectal cancer

Vermeulen, Peter; Eynden, Gert G. Van den; Huget, P.; Goovaerts, G; Weyler, Joost; Lardon, Filip; Marck, E. Van; Hubens, Guy; Dirix, L.

doi:10.1038/sj.bjc.6690051

Cited by 130 publications

(92 citation statements)

References 39 publications

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“…Tomisaki et al (1996), in assessing an association correlation between MVD and liver metastasis, found a mean MVD of 64 in colorectal cancer patients with hepatic metastasis compared with a mean MVD of 52 in patients without metastasis (P ¼ 0.001). In addition, the relationship in colorectal cancer between MVD and prognosis has also been described in most studies indicating a positive correlation between high MVD and poor outcome (Vermeulen et al, 1999;Li et al, 2003). We have shown a direct relationship between increasing MVD and cancer-specific survival.…”

Section: Discussionmentioning

confidence: 49%

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

et al. 2009

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The hypoxia-mediated response of tumours is a major determining factor in growth and metastasis. Understanding tumour biology under hypoxic conditions is crucial for the development of antiangiogenic therapy. Using one of the largest cohorts of rectal adenocarcinomas to date, this study investigated hypoxia-inducible factor-1a (HIF-1a) and HIF-2a protein expression in relation to rectal cancer recurrence and cancer-specific survival. Patients (n ¼ 90) who had undergone surgery for rectal adenocarcinoma, with no prior neoadjuvant therapy or metastatic disease, and for whom adequate follow-up data were available were selected. Microvessel density (MVD), HIF-1a and HIF-2a expressions were assessed immunohistologically with the CD34 antibody for vessel identification and the NB100-131B and NB100-132D3 antibodies for HIF-1a and HIF-2a, respectively. In a multifactorial analysis, results were correlated with tumour stage, recurrence rate and long-term survival. Microvessel density was higher across T and N stages (Po0.001) and associated with poor survival (hazard ratio (HR) ¼ 8.7, Po0.005) and decreased disease-free survival (HR ¼ 4.7, Po0.005). hypoxia-inducible factor-1a and -2a were expressed in 450% of rectal cancers (HIF-1a, 54%, 48/90; HIF-2a, 64%, 58/90). HIF-1a positivity was associated with both TNM stage (Po0.05) and vascular invasion (Po0.005). In contrast, no associations were shown between HIF-2a expression and any pathological features, and HIF-1a positivity had no effect on outcome. The study showed an independent association between HIF-1a expression and advanced TNM stage with poor outcome. Our results indicate that HIF-1a, but not HIF-2a, might be used as a marker of prognosis, in addition to methods currently used, to enhance patient management.

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Section: Discussionmentioning

confidence: 49%

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

et al. 2009

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“…It has already been demonstrated that neovascularization is associated with tumor growth and that the possibility exists that tumors with greater numbers of microvessels are related to metastases 16,17,18 . In fact, a relationship between the degree of microvessel density and worse prognosis for colorectal cancer has been observed in several studies 4,5,19 , although this has not been confirmed by some other authors 20,21,22 . These differences in results have been attributed in part to limitations in the traditional method for assessing angiogenesis 7,8,23 .…”

Section: Discussionmentioning

confidence: 80%

“…Oxaliplatin, bevacizumab and cetuximab are some of these drugs which have been recently approved and recognized as effective in enhancing the results of chemotherapy for colon cancer. An association between the degree of angiogenesis expression and the prognosis for colorectal adenocarcinoma cases has also been reported 3,4,5 . A recent review on histomorphological aspects of angiogenesis and neoangiogenesis has shown that a judicious combination of microscopic angiogenic parameters should be an integral component of tumor staging system 6 .…”

Section: Introductionmentioning

confidence: 78%

Assessment of angiogenesis expression and its relationship with prognosis of colorectal cancer by conventional and computer-assisted histopathological image analysis

et al. 2006

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Assessment of angiogenesis expression and its relationship with prognosis of colorectal cancer by conventional and computer-assisted histopathological image analysis 1Investigação da expressão da angiogênese e sua relação com o prognóstico do câncer colorretal pela análise convencional e informatizada da imagem histopatológica ABSTRACT Purpose:To quantify the degree of angiogenesis by conventional method (microvessel density, MVD) and computerized method (endothelial area, EA), and to evaluate their relationships with the prognosis of patients operated on for colorectal adenocarcinoma. Methods: Tumoral angiogenesis was studied by means of an immunohistochemical technique, using CD 34, on 126 patients; to quantify the angiogenesis, MVD (defined as number of microvessels per mm 2 ) and EA measurement (defined as the area occupied by EA in the microscope field). A computerized method, IMAGELab software was utilized to quantify endothelial area. Results: The mean number of microvessels was 128.6 MV/mm 2 (SD = 44.5) and the mean EA was 4.3% (SD = 2.1). The Pearson method demonstrated a low correlation coefficient between MVD and EA (r = 0.429). No relationship between MVD and EA was observed with regard to relapse-free interval and overall survival. Conclusion:The histological analysis of angiogenesis expression in patients with colorectal adenocarcinoma can be performed either by computer-assisted image analysis of endothelial area or by conventional microvessels counting. Both methods did not show any significant relationship between these angiogenesis parameters with relapse-free interval and overall survival. Key words: Colonic Neoplasms. Image Processing. Computer-Assisted. Prognosis. RESUMOObjetivo: Quantificar a intensidade da angiogênese pelo método convencional (densidade microvasal, DMV) e pelo método informatizado, área endothelial (AE) e avaliar a sua correlação com o prognóstico de doentes operados por adenocarcinoma colorretal. Métodos: A angiogênese tumoral foi investigada por meio de técnica imuno-histoquímica, utilizando-se CD-34, em 126 doentes; para quantificar a angiogênese, a microdensidade vascular, definida como o número de microvasos por mm 2 e a medida da área endotelial, definida como a área ocupada pelo endotélio vascular identificada no campo microscópico foram empregadas. Um programa computadorizado, o IMAGELab foi empregado para a quantificação da área endothelial. Resultados: A media do número de microvasos foi de 128,6 MV/mm 2 (d esvio padrão de 44,5). O método do coeficiente de Pearson demonstrou uma baixa correlação entre a DMV e a AE (r=0,429). Nenhuma correlação entre a DMV e AE com o intervalo livre de doença e tempo global de sobrevida foi observada. Conclusão: A análise histológica da expressão angiogênica em doentes com adenocarcinoma colorretal pode ser realizada tanto da forma informatizada, na quantificação da área endotelial, como pela convencional, na contagem dos microvasos. Ambos métodos não demonstraram relação estatisticamente significante entre estes parâmetros de an...

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“…VEGF expression in primary CRC seems clearly associated with increased chances of dissemination. Moreover, increased VEGF in the primary tumor has been associated with a poor prognosis as positive tumor expression has been correlated with a twofold increase risk of death and an increased risk of tumor recurrence (Ishigami et al, 1998;Vermeulen et al, 1999).…”

Section: Angiogenesismentioning

confidence: 99%

Metastasis-associated Factors Facilitating the Progression of Colorectal Cancer

Zhang

Chen²,

Ding³

2012

Asian Pacific Journal of Cancer Prevention

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Tumor metastasis remains the principal cause of treatment failure and poor prognosis in patients with colorectal cancer. It is a multistage process which includes proteolysis, motility and migration of cells, proliferation in a new site, and neoangiogenesis. A crucial step in the process of intra-and extra-vasation is the activation of proteolytic enzymes capable of degrading the extracellular matrix (ECM). In this stage, urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinases (MMPs) are necessary. Micrometastases need the presence of growth factor and vascular growth factor so that they can form macrometastasis. In addition, cell adhesion molecules (CAMs) and guanine nucleotide exchange factors (GEFs) play important roles in the progression of colorectal cancer and metastatic migration. Further elucidation of the mechanisms of how these molecules contribute will aid in the identification of diagnostic and prognostic markers as well as therapeutic targets for patients with colorectal metastasis.

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Prospective study of intratumoral microvessel density, p53 expression and survival in colorectal cancer

Cited by 130 publications

References 39 publications

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

Assessment of angiogenesis expression and its relationship with prognosis of colorectal cancer by conventional and computer-assisted histopathological image analysis

Metastasis-associated Factors Facilitating the Progression of Colorectal Cancer

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