Angiogenesis in hepatocellular carcinoma as evaluated by CD34 immunohistochemistry

Abstract

To clarify the relationship between angiogenesis and hepatocarcinogenesis on progression of hepatocellular carcinoma (HCC), we quantitatively evaluated angiogenesis by CD34 immunohistochemistry in liver cirrhosis (LC), adenomatous hyperplasia (AH), and HCC, and proliferative activity estimated by Ki-67 immunohistochemistry. Angiogenesis was evaluated by CD34 immunohistochemistry using monoclonal antibody HPCA-2, and tumor proliferative activity was evaluated using monoclonal antibody MIB-1. We used an image analysis system to assess the microvessel density as the area percentage of the endothelial area. Angiogenesis was generally observed in HCC and there was no significant difference among all clinical stages and histological grades of HCC. On the other hand, the staining of CD34 was partly observed in sinusoids of AH, although no positive staining was seen in any sinusoids of LC. The proliferative activity was significantly correlated with the clinical stage and histological grade of HCC. Our results indicate that the quantitation of angiogenesis does not provide significant prognostic information in HCC, but that it may have diagnostic value in distinguishing HCC from non-HCC. Meanwhile, AH, which is not morphologically diagnosed as cancer, shows positive staining for CD34, suggesting that some portion of AH contains cancerous characteristics.

Contrast-enhanced ultrasound in the diagnosis of hepatocellular carcinoma

“…The progression from macroregenerative nodule, to low-grade DN, to high-grade DN, to frank HCC, is characterized by loss of visualization of portal tracts and development of new arterial vessels, termed non-triadal arteries, which becomes the dominant blood supply in overt HCC lesions [19][20][21]. This arterial neoangiogenesis is the landmark of HCC and is the key for imaging diagnosis [22,23].…”

CD34 Expression in Noncancerous Liver Tissue Predicts Multicentric Recurrence of Hepatocellular Carcinoma

“…However, in chronic liver disease, intrahepatic angiogenesis and sinusoidal remodeling occurs, characterized by the deposition of a basement membrane, loss of sinusoidal endothelial fenestrae, and by the expression of CD34, which is commonly referred to as the ‘capillarization' of sinusoids [21,22]. Angiogenesis of chronic liver disease evaluated by CD34 positivity is correlated with the degree of fibrosis [23], and strong staining was reported in HCC and hepatocellular adenoma [24,25,26,27]. Ohmori et al [28,29] reported that high expression of CD34-positive sinusoidal endothelial cells was a risk factor for developing HCC in HCV and HBV chronic hepatitis patients using liver biopsy specimens.…”

Anti-angiogenic Therapy on Hepatocellular Carcinoma Development and Progression

“…Four fields in the cancerous region were observed. After these fields were identified at a magnification of 3200 using a Zeiss Axiovision 2.05 (Hallberg Moos, Germany), the results were analyzed with NIH Image software (NIH, Bethesda, MD) [10]. Briefly, we measured the percentage of 3.3'-diaminobenzidine (DAB)-stained microvessels in the unit frame and calculated the mean value as the MVD [11].…”