Comparative significance of p53 and WAF/1-p21 expression on the efficacy of adjuvant chemotherapy for resectable invasive ductal carcinoma of the pancreas.
p53 tumor-suppressor gene has a dual role as a trigger of apoptosis and as an initiator of DNA repair. The cyclin-dependent kinase inhibitor WAF/1-p21 is induced by wild-type p53 and has been implicated as a downstream mediator of the growth-suppressing and apoptosis-promoting function of wild-type p53, suggesting an impact on the effectiveness of chemotherapy. This study was designed to assess the significance of p53 and WAF/1-p21 expression in the prognosis of patients and the efficacy of adjuvant chemotherapy for resectable invasive ductal carcinoma (IDC) of the pancreas. A total of 58 patients with primary IDC of the pancreas underwent pancreatectomy between 1982 and 1996: 28 patients underwent surgery alone, and 30 patients received postsurgical adjuvant chemotherapy. p53 and WAF/1-p21 were stained immunohistochemically with anti-p53 monoclonal antibody (mAb) and anti-WAF/1-p21 mAb. p53 was positively expressed in 29 (50%) of 58 primary lesions, and p21 was expressed in 24 (41%) lesions; however, p21 expression did not necessarily correlate with p53 expression. The survival curve of the patients with p53(+) IDC was significantly lower than that of those with p53(-) IDC, and p21(+) patients showed a higher survival curve than did p21(-) patients, but this difference was not statistically significant. When p53 and p21 expression were analyzed in combination, the patients with p53(+)p21(-) IDC were found to have a significantly poorer prognosis than others. On the other hand, the survival curve of the adjuvant chemotherapy group was also higher than that of the surgery-alone group, but this difference was not significant. In a multivariate analysis, p21 expression was a significantly low risk factor for death due to IDC overall, and adjuvant chemotherapy was found to decrease the risk of death from IDC in p53(+) patients. Evaluation of expression of p53 and WAF/1-p21 may be beneficial in the prediction of the patient's prognosis as well as prediction of the effects of adjuvant chemotherapy in pancreatic cancer patients.
Nio
Y
Y
First Department of Surgery, Shimane Medical University, Izumo, Japan.
Dong
M
M
Uegaki
K
K
Hirahara
N
N
Minari
Y
Y
Sasaki
S
S
Takamura
M
M
Iguchi
C
C
Tamura
K
K
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010180:Pancreatectomy; D010183:Pancreatic Ducts / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53