Microvessel Morphology and Vascular Endothelial Growth Factor Expression in Human Colonic Carcinoma With or Without Metastasis

Tsuji, Takeshi; Sasaki, Yoshihiro; Tanaka, Masanori; Hanabata, Norihiro; Hada, Ryukichi; Munakata, Akihiro

doi:10.1038/labinvest.3780450

Cited by 41 publications

(40 citation statements)

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“…It has been reported that CD34 is expressed both in blood vessels and lymphatics, but blood vessels stain more intensely. 24,25,36 Thus, the total number of vessels we counted may be an underestimation of the true value. However, this did not bias our findings, as evident from sensitivity analyses.…”

Section: Discussionmentioning

confidence: 99%

“…We counted the total number of vessels (both blood and lymphatic) using the pan-endothelial marker CD34. 24,25 A monoclonal antibody raised against podoplanin, as described previously 26,27 (kindly provided by Dr Geleff, Department of Pathology, University of Vienna, Austria), and the commercial monoclonal antibody D2-40 (SIG-730, Signet Laboratories, Dedham, MA, USA, dilution 1:40) were used to stain lymphatic vessels in two adjacent sections. Immunohistochemistry was performed using the EnVision System (DAKO, Copenhagen, Denmark), as previously described.…”

Section: Tissue Samplesmentioning

confidence: 99%

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Comparison of the diagnostic accuracy of lymphatic endothelium markers: Bayesian approach

2005

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Tumor lymphatic density is evaluated by means of specific lymphatic endothelium markers, and is a potential predictor of clinically meaningful outcomes. There are many claims on the postulated superiority of some of these markers to identify lymphatics, always in the absence of quantitative data. We therefore compared the diagnostic accuracy of the antibody against podoplanin and the commercially available D2-40, employing Bayesian statistics to account for the absence of a gold standard. We used the pan-endothelial marker CD34 to identify 23 542 distinct blood and lymphatic vessels in sections from 30 formalin-fixed, paraffin-embedded archival tissue blocks of head and neck squamous cell carcinoma specimens. We stained two adjacent sections with podoplanin and D2-40 and identified the continuum of each stained vessel in the sections with a comprehensive method. Overall, 1864 vessels were stained with both markers, 119 only with podoplanin and 391 only with D2-40. Significantly more vessels with intraluminal red blood cells were stained with D2-40 compared to podoplanin (McNemar's Po0.0001). Both antibodies had extremely high specificity (99.7% (95% credible interval (CrI): 99.5-99.9%) and 98.8% (95% CrI: 98.3-99.5%) for podoplanin and D2-40, respectively) and very high sensitivity (92.6% (95% CrI: 86.1-97.9%) and 97.3% (95% CrI: 94.9-99.2%) for podoplanin and D2-40, respectively). Inferences were qualitatively similar when we took into account in the analyses the possibility that the two tests (antibodies) may be correlated. We calculated that 96.3% (95% CrI: 94.2-98.6%) of the vessels stained with podoplanin and 88.9% (95% CrI: 83.9-95.7%) of the vessels stained with D2-40 were truly lymphatics. These numbers were in agreement with the observed number of stained vessels without intraluminal red blood cells. Our results suggest that both antibodies are excellent lymphatic endothelium markers and that there may be little reason to prefer either of them in most settings.

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Section: Discussionmentioning

confidence: 99%

Section: Tissue Samplesmentioning

confidence: 99%

Comparison of the diagnostic accuracy of lymphatic endothelium markers: Bayesian approach

2005

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“…VEGF peptide (VEGF [A-20]: sc-152 P; Santa Cruz Biotechnology) was used for VEGF neutralization. As positive human control tissues, tonsil, rheumatoid arthritis synovium, and colon tumor were used (30)(31)(32).…”

Section: Expression Of Vegf In Polymyositis and Dermatomyositismentioning

confidence: 99%

Vascular endothelial growth factor is highly expressed in muscle tissue of patients with polymyositis and patients with dermatomyositis

Grundtman¹,

Tham²,

Ulfgren³

et al. 2008

Arthritis & Rheumatism

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Objective. To investigate the expression of vascular endothelial growth factor (VEGF) in muscle biopsy specimens and serum from patients with polymyositis and patients with dermatomyositis compared with that in healthy control subjects.Methods. Muscle biopsy specimens from 33 patients with polymyositis or dermatomyositis and 15 healthy control subjects and serum samples from 56 patients and 56 healthy control subjects were analyzed. Patients were categorized into 3 groups, depending on disease duration and the presence or absence of inflammatory infiltrates. The expression of VEGF and the vessel marker CD31 in muscle was analyzed by immunohistochemistry, the expression of VEGF messenger RNA (mRNA) was analyzed by in situ hybridization, and serum levels of VEGF were determined by enzymelinked immunosorbent assay.Results. Patients with polymyositis or dermatomyositis in the early or chronic phase without inflammatory infiltrates had a decreased total number of capillaries compared with healthy individuals. In patients with early disease without inflammatory infil-

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“…These differences in results have been attributed in part to limitations in the traditional method for assessing angiogenesis 7,8,23 . Among other factors involved, it can be mentioned that, with the conventional method, only the number of microvessels is evaluated, while other information like the size of the vessels, for example, is disconsidered 11 . This forms the justification for the present study.…”

Section: Discussionmentioning

confidence: 99%

“…The conventional way of quantifying angiogenesis consists of the counting of microvessels on a histological thin section. Lately computerized analysis of histological images have allowed the measurement of vascular parameters, and several studies have also reported a relationship between prognosis and angiogenesis expression 9,10,11 . The aim of the current study was to examine the relationship between angiogenesis and prognosis of colorectal cancer either by manual counting of microvessels density or by computer-assisted analysis of endothelial area.…”

Section: Introductionmentioning

confidence: 99%

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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Microvessel Morphology and Vascular Endothelial Growth Factor Expression in Human Colonic Carcinoma With or Without Metastasis

Cited by 41 publications

References 24 publications

Comparison of the diagnostic accuracy of lymphatic endothelium markers: Bayesian approach

Comparison of the diagnostic accuracy of lymphatic endothelium markers: Bayesian approach

Vascular endothelial growth factor is highly expressed in muscle tissue of patients with polymyositis and patients with dermatomyositis

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

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