Evaluation of angiogenesis in hepatocellular carcinoma: can CD34 discriminate between benign and malignant hepatic lesions

ABSTRACT

Capillarization of hepatic sinusoids is a well recognized phenomenon occurring in hepatocellular carcinoma [HCC]. The endothelial cell marker CD34 has been used for assessment of sinusoid-like neoangiogenesis in HCC as the normal hepatic sinusoids are CD34 negative. The immunohistochemical staining pattern characteristic for HCC using CD34 was compared with those of other hepatic lesions to determine if this stain can be used as a diagnostic tool especially in small samples of core needle biopsies [CNB]. Thirty excisional specimens [showing 20HCC, 20 cirrhotic nodules, 11 dysplastic nodules, 2 metastatic nodules and 4 normal liver] and 15 CNB [including 5 problematic cases] were included in the study. An immunohistochemical evaluation was performed by the standard avidin-biotin-peroxidase complex method with CD34. The sinusoids of normal liver showed no immunoreactivity. Diffuse and strong staining was observed in the overall HCC whereas, cirrhotic and low grade dysplastic liver tissues showed no or focal immunoreactivity in the periportal sinusoids. An increased immunoreactivity was observed with high grade dysplasia. No staining was noticed in metastatic nodules. The same staining pattern were observed in the 10 CNB studied and this was helpful in the 5 problematic cases. CD34 negative staining aided in the correct diagnosis of non-neoplastic lesion in 2 cases where the diagnosis was between well differentiated HCC and non-neoplastic lesion. The diffuse staining pointed to the diagnosis of HCC in the 3 cases in which metastases could not be ruled out. CD34 diffuse positive staining is a useful ancillary tool to support diagnosis of HCC especially in CNB and to distinguish it from non-neoplastic and metastatic lesions