The clinical significance of p21(WAF1/CIP-1) and p53 expression in pancreatic adenocarcinoma.
BACKGROUND
Wild-type p53 protein activates the WAF1/CIP-1 (p21) gene, leading to G1 arrest after DNA damage. The authors investigated the relation of p21 and p53 expression in pancreatic adenocarcinomas to disease stage, overall patient survival, and survival when chemotherapy or radiation therapy was given.


METHODS
Paraffin embedded tissue sections of 75 ductal adenocarcinomas of the pancreas were immunostained for p53 and p21. Nuclear expression was scored as absent, focal (<10%), moderate (10-50%), or strong or diffuse (>50%).


RESULTS
The median survival of patients whose pancreatic tumors expressed the p21 protein (43 of 75 cases, 57%) was better than that for patients whose tumors were p21 negative (32 of 75 cases, 43%) (median survival, 13.5 vs. 9.8 months, respectively; P = 0.23). No difference in survival was found with regard to p53 protein expression (43 of 75 cases, 57%); however, strong p53 expression was significantly associated with advanced disease stage (70% in Stage IV vs. 13-28% in lower stages). Expression of p21 correlated with earlier clinical stage. Stage specific comparisons showed a trend toward increased survival among p21 positive tumor patients diagnosed at clinical Stages I and III but not among those diagnosed at Stage IV. Adjuvant chemotherapy or radiation improved survival significantly if tumors expressed p21 or no p53.


CONCLUSIONS
Expression of p21 is significantly associated with earlier clinical stage in pancreatic adenocarcinoma, perhaps accounting for the better survival observed in this patient group than among those whose tumors were p21 negative. Improved survival with either chemotherapy or radiation therapy was observed for patients whose tumors were p21 positive or p53 negative.
Dergham
S T
ST
Department of Pathology, Wayne State University School of Medicine, Harper Hospital, Detroit, Michigan 48201, USA.
Dugan
M C
MC
Joshi
U S
US
Chen
Y C
YC
Du
W
W
Smith
D W
DW
Arlauskas
P
P
Crissman
J D
JD
Vaitkevicius
V K
VK
Sarkar
F H
FH
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53