Immunohistochemical expression of receptor-tyrosine kinase c-kit protein and TGF-beta1 in invasive ductal carcinoma of the pancreas.
BACKGROUND
The receptor tyrosine kinase c-kit is known to play an important role in the progression of gastrointestinal stromal tumors, but its biological significance in other solid malignancies is unclear. Recent publications have suggested a regulatory role for TGF-beta1 in c-kit-mediated cell growth. The present study assessed the clinicopathological significance of c-kit protein (KIT) and TGF-beta1 expression in resectable invasive ductal carcinomas (IDCs) of the pancreas.


METHODS
This study included 91 pancreatic IDC patients who received a pancreatectomy between 1982 and 2003. The expression of KIT and TGF-beta1 was analyzed by immunohistochemistry.


RESULTS
KIT and TGF-beta1 were expressed in 77% (70/91) and 59% (54/91) of the IDC, respectively. The expression of KIT was not correlated with that of TGF-beta1. TGF-beta1 expression correlated inversely with nodal involvement, but KIT expression did not correlate with any clinicopathological factors. KIT expression had no significant influence on the survival of the patients, whereas the survival rate of TGF-beta1 (+) IDC patients was significantly higher than that of TGF-beta1 (-) IDC patients. Co-expression analysis of KIT and TGF-beta1 indicated that, in patients with KIT (+) IDC, the TGF-beta1 (+) group showed a significantly better survival rate than the TGF-beta1 (-) group. Neither KIT expression nor TGF-beta1 expression had a significant effect on the efficacy of adjuvant chemotherapy (ACT). In multivariate analysis, TGF-beta1 expression was one of the significant variables for survival in IDC patients overall, but KIT expression was not.


CONCLUSIONS
TGF-beta1 expression is suggested to have a significant influence on c-kit-mediated cell proliferation in human pancreatic IDCs.
Nio
Yoshinori
Y
Department of Cardiovascular and Digestive Surgery, Shimane University School of Medicine, Izumo, Shimane 693-8501, Japan. fsurgery@med.shimane-u.ac.jp
Omori
Hiroshi
H
Hashimoto
Koji
K
Itakura
Masayuki
M
Koike
Makoto
M
Yano
Seiji
S
Toga
Tomoko
T
Higami
Tetsuya
T
Maruyama
Riruke
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019009:Proto-Oncogene Proteins c-kit