Expression and diagnostic evaluation of the human tumor-associated antigen RCAS1 in pancreatic cancer.
BACKGROUND
Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is one of the membrane molecules expressed on human cancer cells and is presumed to play a protective role for tumor cells against immune surveillance by inhibition of clonal expansion and induction of cell death in immunocytes.


OBJECTIVE
To address whether RCAS1 is expressed in pancreatic cancer and whether serologic diagnostic evaluation is useful compared with that of carbohydrate antigen 19-9 (CA19-9) and soluble Fas ligand.


METHODS
Immunohistochemical expression of RCAS1 was examined by staining with a 22-1-1 monoclonal antibody, and serum RCAS1 concentrations were determined by an enzyme-linked immunosorbent assay in 20 cases of ductal adenocarcinoma of the pancreas and other pancreatic diseases.


RESULTS
Immunohistochemically, RCAS1 detection occurred in 100% (20/20) of ductal adenocarcinoma of the pancreas cases, 100% (6/6) of intraductal papillary-mucinous adenoma of the pancreas cases, and 40% (2/5) of chronic pancreatitis cases. RCAS1 was found in the cytoplasm of cancer cells and ductal cells. Serum RCAS1 concentrations in patients with ductal adenocarcinoma of the pancreas were significantly higher than those in patients with chronic pancreatitis (p < 0.0001), acute pancreatitis (p < 0.005), and autoimmune pancreatitis (p < 0.001). RCAS1 concentrations in patients with intraductal papillary-mucinous adenoma of the pancreas were also significantly higher than those in patients with chronic pancreatitis (p < 0.05) and autoimmune pancreatitis (p < 0.05). Positive serum RCAS1 samples (concentration, > or = 10 U/mL) were found most often in cases of pancreatic neoplasm (80% [16/20], ductal adenocarcinoma of the pancreas; and 60% [3/5], intraductal papillary-mucinous adenoma of the pancreas). By contrast, in cases of pancreatic inflammatory diseases, raised concentrations occurred in 9.4% (3/32) of chronic pancreatitis cases, none (0/6) of acute pancreatitis cases, and none (0/8) of autoimmune pancreatitis cases. The sensitivity of CA19-9 for ductal adenocarcinoma of the pancreas was 75% and the specificity was 73.1% compared with chronic pancreatitis. On the other hand, the sensitivity of RCAS1 for ductal adenocarcinoma of the pancreas was 80% and the specificity was 96.2% compared with chronic pancreatitis. The specificity of RCAS1 for chronic pancreatitis was higher than that of CA19-9. Serum soluble Fas ligand concentrations were not considerably different among these patients.


CONCLUSIONS
RCAS1 was highly expressed in ductal adenocarcinoma of the pancreas, and serum RCAS1 concentrations in patients with ductal adenocarcinoma of the pancreas were significantly higher than those in patients with other inflammatory pancreatic diseases. Our results indicate that serum RCAS1 concentrations could be a new marker in screening procedures for pancreatic cancer.
Akashi
Tetsuro
T
Department of Medicine, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Oimomi
Hideki
H
Nishiyama
Ken-ichi
K
Nakashima
Manabu
M
Arita
Yoshiyuki
Y
Sumii
Toshihiko
T
Kimura
Toshinari
T
Ito
Tetsuhide
T
Nawata
Hajime
H
Watanabe
Takeshi
T
D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood* / Q000276:immunology / Q000378:metabolism*; D018395:CA-19-9 Antigen; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000378:metabolism; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D010195:Pancreatitis / Q000175:diagnosis
D000951:Antigens, Neoplasm; D018395:CA-19-9 Antigen; C120762:EBAG9 protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins