Faculty Collaboration Database

p21WAF1 expression is associated with improved survival after adjuvant chemoradiation for pancreatic cancer. Surgery 2000 Oct;128(4):520-30

Date

10/03/2000

Pubmed ID

11015084

DOI

10.1067/msy.2000.108052

Scopus ID

2-s2.0-0033624679 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

BACKGROUND: Cell cycle arrest after DNA damage is partly mediated through the transcriptional activation of p21(WAF1) by the p53 tumor suppressor gene. p21(WAF1) and p53 are both critical in maintaining cell cycle control in response to DNA damage from radiation or chemotherapy. Therefore, we examined the role of p21(WAF1) and p53 in the determination of outcome for patients who receive radiation and/or chemotherapy for pancreatic cancer.

METHODS: p21(WAF1) and p53 protein expression were determined (with the use of immunohistochemistry) in specimens from 90 patients with pancreatic cancer. Forty-four patients underwent surgical resection, and 46 patients had either locally unresectable tumors (n = 9 patients) or distant metastases (n = 37 patients). Seventy-three percent of the patients who underwent resection and 63% of the patients who did not undergo resection received radiation and/or chemotherapy.

RESULTS: p21(WAF1) expression was present in 48 of 86 tumors (56%) and was significantly (P<.05) associated with advanced tumor stage. Median survival among patients with resected pancreatic cancer who received adjuvant chemoradiation with p21(WAF1)-positive tumors was significantly longer than in patients with no p21(WAF1) staining (25 vs. 11 months; P = .01). Fifty of 89 tumors (56%) stained positive for p53 protein. p53 overexpression was associated with decreased survival in patients who did not undergo resection.

CONCLUSIONS: Normal p21(WAF1) expression may be necessary for a beneficial response to current adjuvant chemoradiation protocols for pancreatic cancer. Alternate strategies for adjuvant therapy should be explored for patients with pancreatic cancer who lack functional p21(WAF1).

Author List

Ahrendt SA, Brown HM, Komorowski RA, Zhu YR, Wilson SD, Erickson BA, Ritch PS, Pitt HA, Demeure MJ

Author

Beth A. Erickson MD Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Aged
Biomarkers, Tumor
Combined Modality Therapy
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
Female
Humans
Immunohistochemistry
Male
Middle Aged
Multivariate Analysis
Pancreatectomy
Pancreatic Neoplasms
Prognosis
Proportional Hazards Models
Survival Analysis
Tumor Suppressor Protein p53