Expression of retinoblastoma and p53 pathway-related proteins in resectable invasive ductal carcinoma of the pancreas: potential cooperative effects on clinical outcome.
BACKGROUND
The retinoblastoma protein (RB) is an important cell cycle regulator. RB also plays an important role in the regulation of apoptosis, which is mediated by interaction of p53 signaling mediators. The present study was designed to assess the clinicopathological significance of RB and p53 pathway-related proteins (p53, p21WAF1/CIP1 and Bax) expression in resectable invasive ductal carcinoma (IDC) of the pancreas.


METHODS
The present study included 79 pancreatic IDC patients, who received surgery between 1982 and 2002. The expression of RB and p53 pathway-related proteins (p53, p21WAF1/CIP1 and Bax) were analyzed by immunohistochemistry.


RESULTS
RB was expressed in 45 (57%) of the 79 patients. RB expression correlated significantly with histological grade and grade of nodal involvement. The positive rate of p53, p21WAF1/CIP1 and Bax expression was 49%, 48% and 67%, respectively. RB expression alone did not have a significant effect on patient survival. However, coexpression analysis of RB and p53 pathway-related proteins indicated that, in the patients with RB (+) IDC, the p21WAF1/CIP1 (+) group had a significantly higher survival rate than the p21WAF1/CIP1 (-) group. On the other hand, in the patients with RB (-) IDC, the Bax (+) group had a significantly higher survival rate than the Bax (-) group. Multivariate analysis indicated that, in the RB (-) group, pTNM stage, adjuvant chemotherapy and Bax expression were significant variables.


CONCLUSIONS
The evaluation of RB expression combined with the mediators of the p53 pathway, p21WAF1/CIP1 and Bax, may provide more accurate information regarding clinical outcome, beyond that which is provided by RB expression alone.
Hashimoto
Koji
K
Department of Cardiovascular and Digestive Surgery, Shimane University School of Medicine, Izumo 693-8501, Japan. kohashim@med.shimane-u.ac.jp
Nio
Yoshinori
Y
Koike
Makoto
M
Itakura
Masayuki
M
Yano
Seiji
S
Higami
Tetsuya
T
Maruyama
Riruke
R
D000328:Adult; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015996:Survival Rate; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein