Vascular Immunohistochemical Markers: Contributions to Hepatocellular Nodule Diagnosis in Explanted Livers

Nascimento, Cristina Moreira do; Caroli-Bottino, Adriana; Paschoal, Juliana Passos; Pannain, Vera Lúcia

doi:10.1016/j.transproceed.2009.09.068

Cited by 12 publications

(7 citation statements)

References 10 publications

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“…Angiogenesis in liver diseases is peculiar because immunophenotype changes of endothelial sinusoidal cells occur in cirrhosis, causing cells to express vascular markers not found in normal livers. They are also observed in precancerous lesions and are considered part of the hepatocarcinogenesis process [24,25]. …”

Section: Discussionmentioning

confidence: 99%

Microvascular density of regenerative nodule to small hepatocellular carcinoma by automated analysis using CD105 and CD34 immunoexpression

et al. 2014

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BackgroundAngiogenesis is a proliferative process resulting in the development of new blood vessels from existing endothelial cells and is considered crucial for tumor growth and metastasis. Tumor angiogenesis can be quantified by microvascular density (MVD), which is evaluated in highly vascularized tumor areas (hot spots) by immunohistochemical assays using CD34 and CD31 pan-endothelial antibodies. More recently, CD105 has been successfully used for some tumor types because it could discriminate neovascularization. The expression of CD34 and CD105 in hepatocellular carcinomas (HCC) and hepatic precancerous lesions has been reported—although the results for CD105 are controversial—but to the best our knowledge, CD105 has not been previously investigated in dysplastic nodules (DN). We investigated and compared MVD-CD34 and MVD-CD105 immunoexpression in tissues containing different stages of hepatocarcinogenesis, including DN.MethodsA total of 31 regenerative nodules (RN), 26 DN and 25 small HCC from explants were used for immunohistochemical tests with CD34 and CD105 antibodies. Antibody expression was quantified by computerized image analysis measurement of MVD, areas containing highly positive endothelial cells within the nodules.ResultsThe median MVD for CD34 was higher in HCC than in DN and RN (p < 0.01), and was higher in DN compared with RN (p = 0.033). In contrast, MVD with CD105 was higher in RN, and the difference was significant in RN and DN compared with HCC (p = 0.019 and p = 0.012, respectively). When MVD with CD34 and CD105 were compared within a single group, there was a significant predominance of CD105 in RN and DN (p < 0.01). In addition, MVD-C34 in HCC predominated compared with MVD-CD105, but the difference was not statistically significant (p = 0.128).ConclusionsThis study identified a close relationship between CD105 and liver cirrhosis, and that CD34 antibody is a good endothelial marker for hepatic carcinogenesis. There was no difference between the use of CD105 and CD34 antibodies in preneoplastic lesions.

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Section: Discussionmentioning

confidence: 99%

Microvascular density of regenerative nodule to small hepatocellular carcinoma by automated analysis using CD105 and CD34 immunoexpression

et al. 2014

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“…Likewise, Wang et al 28 demonstrated that an elevated level of VEGF occurred at early stages of rat chemical liver carcinogenesis and increased progressively with the advancement of the carcinogenic process. Furthermore, Park et al 29 and Nascimento et al 30 have reported an aberrant gradual stage-dependent increase in the degree of vascular endothelial growth factor A (VEGFA) and CD34 expression during hepatocarcinogenesis in humans. Figure 5.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic responses provide a new mechanistic basis for the chemopreventive effects of folic acid and tributyrin in rat liver carcinogenesis

Guariento

Furtado

Conti

et al. 2014

Intl Journal of Cancer

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The steady increase in the incidence and mortality of hepatocellular carcinoma (HCC) signifies a crucial need to understand better its pathogenesis to improve clinical management and prevention of the disease. The aim of this study was to investigate molecular mechanisms for the chemopreventive effects of folic acid and tributyrin alone or in combination on rat hepatocarcinogenesis. Male Wistar rats were subjected to a classic “resistant hepatocyte” model of liver carcinogenesis and treated with folic acid and tributyrin alone or in combination for 5 weeks during promotion stage. Treatment with folic acid and tributyrin alone or in combination strongly inhibited the development of glutathione-S-transferase placental form (GSTP)-positive foci. Microarray analysis showed significant changes in gene expression. A total of 501, 655, and 940 of differentially expressed genes, involved in cell cycle, p53-signaling, angiogenesis, and Wnt pathways, was identified in the livers of rats treated with folic acid, tributyrin or folic acid and tributyrin. A detailed analysis of these differentially expressed genes revealed that treatments inhibited angiogenesis in the preneoplastic livers. This was evidenced by the fact that 30 out of 77 differentially expressed genes common to all three treatments are involved in the regulation of the angiogenesis pathway. The inhibition of angiogenesis was confirmed by reduced levels of CD34 protein. In conclusion, the tumor-suppressing activity of folic acid and tributyrin is associated with inhibition of angiogenesis at early stages of rat liver carcinogenesis. Importantly, the combination of folic acid and tributyrin has stronger chemopreventive effect than each of the compounds alone.

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“…Although the histologic differentiation of HGDN and early HCC is difficult,41, 53 recent genetic and immunologic advances show that this differentiation can be performed with high specificity 27‐33, 36, 71. Furthermore, false‐negative diagnosis of HCC due to sampling error may be reduced by obtaining a hepatobiliary phase MRI, although further investigations are needed 6, 37, 40.…”

Section: Discussionmentioning

confidence: 99%

“…When the distinction between HGDN and early HCC was difficult,28 specific immunostaining techniques were assumed to be used 20, 28‐33. In particular, distinction with high specificity was reported by the application of multiple tumor markers on liver biopsy specimens 29‐31, 34‐36. Enhanced dynamic computed tomography (CT) or magnetic resonance imaging (MRI) was obtained in all patients 37‐39.…”

Section: Methodsmentioning

confidence: 99%

Radiofrequency ablation of high-grade dysplastic nodules

Cho¹,

Chung²,

Kim³

et al. 2011

Hepatology

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Vascular Immunohistochemical Markers: Contributions to Hepatocellular Nodule Diagnosis in Explanted Livers

Cited by 12 publications

References 10 publications

Microvascular density of regenerative nodule to small hepatocellular carcinoma by automated analysis using CD105 and CD34 immunoexpression

Microvascular density of regenerative nodule to small hepatocellular carcinoma by automated analysis using CD105 and CD34 immunoexpression

Transcriptomic responses provide a new mechanistic basis for the chemopreventive effects of folic acid and tributyrin in rat liver carcinogenesis

Radiofrequency ablation of high-grade dysplastic nodules

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