MVD is evaluated in highly vascularized tumor areas (hot spots) by immunohistochemical assays using pan-endothelial antibodies (CD34, CD31 and von Willebrand factor)

MVD is evaluated in highly vascularized tumor areas (hot spots) by immunohistochemical assays using pan-endothelial antibodies (CD34, CD31 and von Willebrand factor). expression was quantified by computerized image analysis measurement of MVD, areas containing highly positive endothelial cells within the nodules. Results The 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). Conclusions This 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. strong class=”kwd-title” Keywords: Microvascular density, Regenerative nodule, Dysplastic nodule, Hepatocellular carcinoma, CD105, CD34 Background Angiogenesis is a proliferative process resulting in the development of new blood vessels from existing endothelial cells and occurs during reproduction, development and wound repair. The angiogenic process includes cell migration, proliferation, microvascular differentiation, extracellular matrix degradation and structural reorganization [1]. Folkmans hypothesis that tumor growth is angiogenesis-dependent was confirmed by biological, pharmacological and genetic evidence [2]. Endothelial progenitor cells from bone marrow are recruited to vascular bed tumors and contribute to tumor growth [3]. For years it was thought that the formation of new blood vessels occurred after the cells acquired a malignant phenotype; however, experimental and clinical evidence has demonstrated that angiogenesis is increased in some premalignant lesions in cervical, lung and in adenoma-carcinoma colon cancer sequence [4-6]. It was also observed in the evolution of MGUS (Monoclonal Gammopathy of Undetermined Significance) [7]. Tumor angiogenesis is usually quantified as microvascular density (MVD) [8]. MVD is evaluated in highly vascularized tumor areas (hot spots) by immunohistochemical assays using pan-endothelial antibodies (CD34, CD31 and von Willebrand factor). It is assumed that angiogenic activity is associated with the development and progression of some solid tumors and has an important prognostic value [9-12]. Recently, evidence demonstrated that another endothelial marker, endoglin (CD105), is overexpressed in active angiogenesis and might be a useful marker of neoangiogenesis, because it can discriminate immature vessels from the mature and established vessels [13,14]. Furthermore, endoglin is undetectable or weakly expressed in the endothelium of normal tissues [15]. In liver it was observed in very few endothelium cells in the vicinity of veins [15]. Endoglin is a transmembrane accessory receptor of the transforming growth factor beta receptor system [16] expressed mainly in vascular endothelial cells and is a diagnostic and therapeutic molecular target for cancer. CD105 expression has been detected by immunohistochemistry for the evaluation of Gilteritinib (ASP2215) angiogenesis in premalignant and malignant lesions. It is considered more neoangiogenesis-specific Rabbit Polyclonal to p50 Dynamitin than pan-endothelial Gilteritinib (ASP2215) CD34 and CD31 antibodies and might have a more significant prognostic value for some cancers [14,17,18]. The role of angiogenesis in chronic liver disease, liver premalignant lesions and liver cancer has also been studied using pan-endothelial antibodies [19]. However, studies of endoglin and angiogenesis have been controversial [20,21], and no studies have reported the association between Gilteritinib (ASP2215) endoglin and liver premalignant lesions. The purpose of this study was to determine and compare MVD with CD105 and CD34 antibodies in small hepatocellular carcinomas (HCC), regenerative and dysplastic liver nodules. Methods This study used samples from 31 regenerative nodules (RN), 26 dysplastic nodules (DN) and 25 small HCC from the Department of Pathology/University Hospital, UFRJ. The samples were obtained from 28 patient liver cirrhotic explants who underwent surgery between 2000 and 2007. The explants specimens were 10% buffered-formalin fixed and paraffin-embedded using standard histology methodology to ensure the viability of tissues for further immunohistochemical studies. Lesions were histologically classified according to IWP guidelines [22]. Patients consisted of 16 males and 12 females with a mean age of 55?years. Hepatitis C virus (HCV) infection was the main etiological factor of liver cirrhosis (82.1%), followed by hepatitis B virus (7.1%), alcohol, and biliary and cryptogenic etiologies (3.6%). This study was approved by the local ethics committee (CEP:237/07). Immunohistochemistry Immunohistochemical staining was performed for CD105 and CD34 antibodies in 4?m thick tissue.

---