p21WAF1 expression is associated with improved survival after adjuvant chemoradiation for pancreatic cancer.
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).
Ahrendt
S A
SA
Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Brown
H M
HM
Komorowski
R A
RA
Zhu
Y R
YR
Wilson
S D
SD
Erickson
B A
BA
Ritch
P S
PS
Pitt
H A
HA
Demeure
M J
MJ
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis; D003131:Combined Modality Therapy; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery*; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53