NY-ESO-1 expression and immunogenicity in malignant and benign breast tumors.
NY-ESO-1 is a cancer/testis antigen expressed in normal adult tissues solely in the testicular germ cells of normal adults and in various cancers. It induces specific humoral and cellular immunity in patients with NY-ESO-1-expressing cancer. The aim of this study was to determine the frequency of NY-ESO-1 mRNA and protein expression in malignant and benign breast tumors. NY-ESO-1 mRNA expression was detected by conventional reverse transcription-PCR and real-time PCR, and that of the protein expression by immunohistochemistry and Western blot analysis. Expression of NY-ESO-1 mRNA was detected in 37 of 88 (42%) cancer specimens, whereas that of the NY-ESO-1 protein was detected only in 1 mRNA-positive specimen. In the latter case, expression level of NY-ESO-1 mRNA relative to that in the testis was relatively high (75% of testicular expression) and to the other among breast cancer specimens. In benign breast lesions, 21 of 31 (68%) specimens expressed low levels of NY-ESO-1 mRNA. In 1 case of fibroadenoma, NY-ESO-1 mRNA was 8% of the testicular level, and protein was detected by Western blot analysis. Only 1 breast cancer patient had detectable antibody at time of surgery, which disappeared within 2 years. Tumor specimen from this patient was both NY-ESO-1 mRNA and protein positive, and NY-ESO-1-specific CD8 T cells were detected in this patient by IFN-gamma enzyme-linked immunospot assay using NY-ESO-1 recombinant adeno and vaccinia virus. A higher rate of NY-ESO-1 expression was noted in breast cancer with high histological grade and negative hormone receptor status, suggesting NY-ESO-1 as a potential tumor antigen for immunotherapy in patients with breast cancer and poor prognosis.
Sugita
Yurika
Y
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita-city, Osaka 565-0871, Japan.
Wada
Hisashi
H
Fujita
Shoichiro
S
Nakata
Tetsuya
T
Sato
Shuichiro
S
Noguchi
Yuji
Y
Jungbluth
Achim A
AA
Yamaguchi
Masae
M
Chen
Yao-Tseng
YT
Stockert
Elisabeth
E
Gnjatic
Sacha
S
Williamson
Barbara
B
Scanlan
Matthew J
MJ
Ono
Toshiro
T
Sakita
Isao
I
Yasui
Masayoshi
M
Miyoshi
Yasuo
Y
Tamaki
Yasuhiro
Y
Matsuura
Nariaki
N
Noguchi
Shinzaburo
S
Old
Lloyd J
LJ
Nakayama
Eiichi
E
Monden
Morito
M
D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000912:Antibodies, Neoplasm / Q000097:blood; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes; D044584:Carcinoma, Ductal / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011994:Recombinant Proteins