Genetic detection for micrometastasis in lymph node of biliary tract carcinoma.
The presence of regional lymph node metastasis is one of the most significant poor-prognosis factors in patients with biliary tract carcinoma. To establish a sensitive reverse transcription (RT)-PCR assay to detect micrometastases in lymph nodes of biliary tract carcinoma, we first investigated the optimal markers in biliary tract carcinoma. The expressions of the six candidates for a suitable RT-PCR marker [mammaglobin B, carcinoembryonic antigen (CEA), cytokeratin (CK) 20, prostate-specific antigen, and melanoma antigens (MAGE-1 and MAGE-3)] were evaluated in two bile duct cancer cell lines and human biliary tract carcinoma tissues. Of 32 carcinoma tissues, mammaglobin B, CEA, prostate-specific antigen, MAGE-1, MAGE-3, and CK 20 were expressed in 28 (88%), 26 (81%), 4 (13%), 5 (16%), 7 (22%), and 9 (28%), respectively. Mammaglobin B and CEA were considered to be good markers of the six candidates. We then examined 209 lymph nodes obtained from 15 patients with biliary tract carcinoma by RT-PCR assay using both mammaglobin B and CEA and compared the results with those of histological examination. All of 20 histologically positive lymph nodes for metastasis displayed the PCR product(s) of marker genes. Of 189 histologically negative nodes, 24 (13%) nodes expressed mammaglobin B and/or CEA mRNA, suggesting the presence of micrometastasis. Our findings suggest that mammaglobin B and CEA could be useful RT-PCR markers for the detection of lymph node micrometastases in biliary tract carcinomas. Our RT-PCR assay allows accurate clinical staging necessary for patient stratification with respect to adjuvant therapy after surgery.
Okami
J
J
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Suita-city, Japan.
Dohno
K
K
Sakon
M
M
Iwao
K
K
Yamada
T
T
Yamamoto
H
H
Fujiwara
Y
Y
Nagano
H
H
Umeshita
K
K
Matsuura
N
N
Nakamori
S
S
Monden
M
M
D000368:Aged; D000951:Antigens, Neoplasm; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism; D001661:Biliary Tract Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000096:biosynthesis; D053554:Keratin-20; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008297:Male; D060788:Mammaglobin B; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D009185:Myelin Proteins; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011510:Proteolipids; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060765:Secretoglobins; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014598:Uteroglobin / Q000096:biosynthesis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D018076:DNA, Complementary; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; D053554:Keratin-20; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; D060788:Mammaglobin B; D058950:Melanoma-Specific Antigens; D009185:Myelin Proteins; D009363:Neoplasm Proteins; D011510:Proteolipids; D012333:RNA, Messenger; C556467:SCGB2A1 protein, human; D060765:Secretoglobins; D014598:Uteroglobin; D017430:Prostate-Specific Antigen