Tumor-associated antigen CAPERα and microvessel density in hepatocellular carcinoma

Purpose: CAPER alpha, a tumor-associated antigen, was identified from a cDNA clone with autoantibody from a patient with hepatocellular carcinoma (HCC). It has been implicated, by way of alternative splicing of VEGF pre-mRNA, in the regulation of microvessel formation in Ewing's sarcoma. In this study, we looked for possible association of alterations in CAPER alpha with microvessel density in HCC. Methods: Enzyme-linked immunosorbent assay using recombinant CAPER alpha as antigen were used to detect antibody against CAPER alpha. Immunohistochemistry (IHC) on liver sections was performed to analyze expression profiles of CAPER alpha, VEGF and CD34 in HCC and control tissues and was further used to assess the correlation of expression among CAPER alpha, VEGF and CD34 in HCC development. Results: Autoantibody to CAPER alpha was highest in HCC (22/76, 28.9%), not detected in prostate cancer (0/79) and at 3.4% (3/88) in breast cancer. In immunohistochemical analysis of grades II and III HCC tissues, significantly decreased immunostaining for CAPER alpha was observed and this correlated directly with decreased immunostaining for VEGF (R=0.534, P=0.0003). Using CD34 immunostaining for detecting newly formed microvessels, strong staining was observed in grades II and III HCC. Normal liver sections, all of which have high expression of CAPER alpha were totally negative for CD34 immunostaining. A significant inverse correlation was seen between CAPER alpha and CD34 immunostaining (R=-0.481, P=0.0012). Conclusions: Decreased expression of CAPER alpha appears to be correlated with appearance of microvessels. It would be of interest to elucidate the cause of altered CAPER alpha since new formation of microvessels is important in progression of HCC.