Comparative significance of p53 and WAF/1-p21 expression on the efficacy of adjuvant chemotherapy for resectable invasive ductal carcinoma of the pancreas.

Abstract

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.

• Authors: Y Nio, M Dong, K Uegaki, N Hirahara, Y Minari, S Sasaki, M Takamura, C Iguchi, K Tamura
• Journal: Pancreas (Pancreas) Vol. 18 Issue 2 Pg. 117-26 (Mar 1999) ISSN: 0885-3177 [Print] United States
• PMID: 10090408 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins
• Tumor Suppressor Protein p53

Topics

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Carcinoma (diagnosis, metabolism, mortality, pathology, therapy)
• Chemotherapy, Adjuvant
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins (biosynthesis)
• Female
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Pancreatectomy
• Pancreatic Ducts (pathology)
• Pancreatic Neoplasms (diagnosis, metabolism, mortality, pathology, therapy)
• Prognosis
• Survival Rate
• Tumor Suppressor Protein p53 (biosynthesis)