Immunohistochemical analysis of the expression of FATE/BJ-HCC-2 antigen in normal and malignant tissues.
FATE/BJ-HCC-2 is a newly identified cancer/testis (CT) antigen, which was detected in tumor tissues and testis. As previous studies of FATE/BJ-HCC-2 expression pattern were mainly based on messenger RNA (mRNA) analysis, it is necessary to investigate its actual protein expression pattern in tumor tissues for the evaluation of its application value. In this study, we produced specific polyclonal antibody (pAb) to the recombinant FATE/BJ-HCC-2 protein and analyzed the FATE/BJ-HCC-2 antigen expression in normal and malignant tissues by the immunohistochemical approach. The results showed that there was no detectable FATE/BJ-HCC-2 antigen expressed in normal tissues except testis. In hepatocellular carcinoma (HCC) tissues, the FATE/BJ-HCC-2 antigen was detected in 20% (7/35) specimens. All samples that expressed the FATE/BJ-HCC-2 antigen were of poorly or moderately differentiated HCC. The stained antigen was located in the cytoplasm and the staining pattern showed heterogeneity from focal to more than 40% of the tumor cells. The FATE/BJ-HCC-2 antigen was also expressed in other tumor tissues. The results of [3H]thymidine incorporation showed that FATE/BJ-HCC-2 protein enhanced tumor cell proliferation after transfection of FATE/BJ-HCC-2 gene in HCC cell line (P<0.01). This effect could be specifically blocked by anti-FATE/BJ-HCC-2 pAb. Serological screening showed that the antibody specific to the FATE/BJ-HCC-2 antigen was detected in 7.7% (4/52) patients. Notably, the four positive patients bore poorly or moderately differentiated HCC. FATE/BJ-HCC-2 mRNA transcript was detected in the peripheral blood mononuclear cells (PBMCs) of 46.67% patients whose resected HCC tissue samples were positive for FATE/BJ-HCC-2 mRNA, which implicated tumor cell dissemination in blood circulation and may relate to the metastasis of HCC. Thus, FATE/BJ-HCC-2 may be a valuable candidate CT antigen for polyvalent vaccines in tumor immunotherapy and an assisting diagnostic marker for prognosis of the disease.
Yang
Xiao Ang
XA
Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Dong
Xue Yuan
XY
Qiao
Huan
H
Wang
Yue Dan
YD
Peng
Ji Run
JR
Li
Yan
Y
Pang
Xue Wen
XW
Tian
Chan
C
Chen
Wei Feng
WF
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism*
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; C449758:FATE1 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors