Expression of cancer-testis antigen (CTA) genes in intrahepatic cholangiocarcinoma.
BACKGROUND
Cancer-testis antigens (CTA), such as MAGE, are selectively expressed in various types of human neoplasms but not in normal tissues other than testis. This characteristic feature of CTA makes them promising antigens for cancer-specific immunotherapy.


METHODS
We investigated the expression of five genes, including MAGE-1, MAGE-3, NY-ESO-1, SCP-1, and SSX-4, in 20 surgical samples of intrahepatic cholangiocarcinomas (IHCC) using reverse transcription-polymerase chain reaction. To visualize the localization of MAGE proteins, we performed immunohistochemical studies. Furthermore, the correlation between the CTA expression and DNA methylation status was studied in three bile duct cancer cell lines.


RESULTS
Expression of MAGE-1, MAGE-3, NY-ESO-1, SCP-1, and SSX-4 was recognized in 4, 4, 2, 6, and 3 of all 20 cases, respectively. In contrast, the expressions of five genes were not recognized at all in the corresponding normal tissues. In 10 cases (50%), the tumors expressed at least one of the five CTA. An immunohistochemical analysis of MAGE proteins demonstrated homogenous or focal distributions in cytoplasm of the IHCC. Using a demethylating agent, MAGE-1, NY-ESO-1, SCP-1, and SSX-4 were induced in two of three cell lines, whereas MAGE-3 was not.


CONCLUSIONS
Half of the tumor tissues of IHCC expressed at least one of the CTA. Some of the patients with IHCC, therefore, should be candidates for potentially useful cancer-specific immunotherapy.
Utsunomiya
Tohru
T
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumibaru, Beppu 874-0838, Japan.
Inoue
Hiroshi
H
Tanaka
Fumiaki
F
Yamaguchi
Hiroshi
H
Ohta
Mitsuhiko
M
Okamoto
Masahiro
M
Mimori
Koshi
K
Mori
Masaki
M
D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000096:biosynthesis*; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000276:immunology*; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm