Evaluation And Comparison Of Microvessel Density Using The Markers Cd34 And Cd105 In Regenerative Nodules, Dysplastic Nodules And Hepatocellular Carcinoma


Purpose: The progression of hepatocellular carcinoma (HCC) is multifactorial and angiogenesis plays a fundamental role, mainly because HCC is a highly vascularized tumor. Methods: In this study, we determined microvessel density (MVD) using the immunohistochemical markers, CD34 and CD105 (Endoglin), in 44 hepatectomy specimens, encompassing 44 malignant nodules (HCC), 44 regenerative nodules (RN), and 15 dysplastic nodules (DN). The evaluation included the determination of MVD in all nodules. For statistical analysis, a descriptive analysis was carried out using measurements of position and dispersion for continuous variables; ANOVA was used to compare between groups, considering p < 0.05 as statistically significant. Results: We observed a significant difference when comparing CD34 and CD105 immunoexpression in HCC, DN, and RN. CD105 was predominantly expressed in the peripheral regions in HCC, with mean MVD scores of 6.2 ± 4.1 and 10.7 ± 4.4 at the center and periphery of the nodules, respectively, with significant differences between groups (p < 0.0001). CD34 had higher mean MVD scores than CD105 in HCC, with a more uniform positivity pattern. CD105 immunoexpression in DN exhibited a pattern similar to HCC. However, in RN, CD105 exhibited a higher MVD score in the central portion of the nodules. CD105 was expressed in a subset of newly formed microvessels in HCC and demonstrated an elevated mean MVD in cirrhotic or regenerative nodules. Conclusions: MVD determined by CD34 and CD105 expression may be used as an additional parameter to distinguish benign from malignant liver nodules. © 2014 Asian Pacific Association for the Study of the Liver.82260265Tsukuma, H., Hiyama, T., Tanaka, S., Nakao, M., Yabuuchi, T., Kitamura, T., Nakanishi, K., Kawashima, T., Risk factors for hepatocellular carcinoma among patients with chronic liver disease (1993) New England Journal of Medicine, 328 (25), pp. 1797-1801. , DOI 10.1056/NEJM199306243282501El-Serag, H.B., Rudolph, K.L., Hepatocellular Carcinoma: Epidemiology and Molecular Carcinogenesis (2007) Gastroenterology, 132 (7), pp. 2557-2576. , DOI 10.1053/j.gastro.2007.04.061, PII S0016508507007998Theise, N.D., Park, Y.N., Curado, M.P., Hepatocellular carcinoma (2010) WHO Classification of Tumours of the Digestive System, pp. 205-216. , Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. Lyon: IARC PressTheise, N.D., Park, Y.N., Kojiro, M., Dysplastic nodules and hepatocarcinogenesis (2002) Clinics in Liver Disease, 6 (2), pp. 497-512. , DOI 10.1016/S1089-3261(02)00006-5, PII S1089326102000065Villanueva, A., Newell, P., Chiang, D.Y., Friedman, S.L., Llovet, J.M., Genomics and signaling pathways in hepatocellular carcinoma (2007) Semin Liver Dis, 27 (1), pp. 55-76Pang, R.W., Joh, J.W., Johnson, P.J., Monden, M., Pawlik, T.M., Poon, R.T., Biology of hepatocellular carcinoma (2008) Ann Surg Oncol, 15 (4), pp. 962-971Hytiroglou, P., Morphological Changes of Early Human Hepatocarcinogenesis (2004) Seminars in Liver Disease, 24 (1), pp. 65-75. , DOI 10.1055/s-2004-823097Park, Y.N., Yang, C.-P., Fernandez, G.J., Cubukcu, O., Thung, S.N., Theise, N.D., Neoangiogenesis and sinusoidal 'capillarization' in dysplastic nodules of the liver (1998) American Journal of Surgical Pathology, 22 (6), pp. 656-662. , DOI 10.1097/00000478-199806000-00002Semela, D., Dufour, J.-F., Angiogenesis and hepatocellular carcinoma (2004) Journal of Hepatology, 41 (5), pp. 864-880. , DOI 10.1016/j.jhep.2004.09.006, PII S0168827804003940Deli, G., Jin, C.-H., Mu, R., Yang, S., Liang, Y., Chen, D., Makuuchi, M., Immunohistochemical assessment of angiogenesis in hepatocellular carcinoma and surrounding cirrhotic liver tissues (2005) World Journal of Gastroenterology, 11 (7), pp. 960-963Terminology of nodular hepatocellular lesions (1995) Hepatology, 22 (3), pp. 983-993. , International Working PartyHytiroglou, P., Park, Y.N., Krinsky, G., Theise, N.D., Hepatic Precancerous Lesions and Small Hepatocellular Carcinoma (2007) Gastroenterology Clinics of North America, 36 (4), pp. 867-887. , DOI 10.1016/j.gtc.2007.08.010, PII S0889855307000817, Pathology and Clinical Relevance of Neoplastic Precursor Lesions of the Gastrointestinal Tract, Liver, and Pancreaticobiliary SystemPathologic diagnosis of early hepatocellular carcinoma: A report of the international consensus group for hepatocellular neoplasia (2009) Hepatology, 49 (2), pp. 658-664. , International Consensus Group for Hepatocellular NeoplasiaRoncalli, M., Borzio, M., Di Tommaso, L., Hepatocellular dysplastic nodules (2008) Ann Ital Chir, 79 (2), pp. 81-89Sakamoto, M., Effendi, K., Masugi, Y., Molecular diagnosis of multistage hepatocarcinogenesis (2010) Jpn J Clin Oncol, 40 (9), pp. 891-896Shiraha, H., Yamamoto, K., Namba, M., Human hepatocyte carcinogenesis (2013) Int J Oncol, 42 (4), pp. 1133-1138. , reviewFolkman, J., Tumor angiogenesis: Therapeutic implications (1971) N Engl J Med, 285 (21), pp. 1182-1186Folkman, J., Tumor angiogenesis (1985) Adv Cancer Res, 43, pp. 175-203Folkman, J., Shing, Y., Angiogenesis (1992) J Biol Chem, 267 (16), pp. 10931-10934Frachon, S., Gouysse, G., Dumortier, J., Couvelard, A., Nejjari, M., Mion, F., Berger, F., Scoazec, J.-Y., Endothelial cell marker expression in dysplastic lesions of the liver: An immunohistochemical study (2001) Journal of Hepatology, 34 (6), pp. 850-857. , DOI 10.1016/S0168-8278(01)00049-6, PII S0168827801000496Di, C.I., Fraggetta, F., Lombardo, R., Azzarello, G., Vasquez, E., Puleo, S., CD 34 expression in chronic and neoplastic liver diseases (2002) Panminerva Medica, 44 (4), pp. 365-367Yang, L., Lu, W., Huang, G., Wang, W., Correlation between CD105 expression and postoperative recurrence and metastasis of hepatocellular carcinoma (2006) BMC Cancer, 6, p. 110Nakamura, T., Changes in expression of bile canalicular CD10 and sinusoidal CD105 (endoglina) in peri-tumoral hepatic tissue (2009) Tumori, 95 (4), pp. 495-500Wang, Y., Zhang, X.H., Guo, P., Yan, L.N., He, D., Tumor microvascular density detected by anti-CD105 and anti-CD34 in hepatocellular carcinoma patients and its predictive value of tumor recurrence after liver transplantation (2010) Sichuan Da Xue Xue Bao Yi Xue Ban, 41 (5), pp. 818-882Ho, J.W., Poon, R.T., Sun, C.K., Xue, W.-C., Fan, S.-T., Clinicopathological and prognostic implications of endoglin (CD105) expression in hepatocellular carcinoma and its adjacent non-tumorous liver (2005) World Journal of Gastroenterology, 11 (2), pp. 176-181Yu, D., Zhuang, L., Sun, X., Chen, J., Yao, Y., Meng, K., Particular distribution and expression pattern of endoglin (CD105) in the liver of patients with hepatocellular carcinoma (2007) BMC Cancer, 7, p. 122Wang, Z.S., Wu, L.Q., Yi, X., Geng, C., Li, Y.J., Yao, R.Y., Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-feto-protein after radical hepatectomy (2013) BMC Cancer, 13 (1), p. 30

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