p53 expression in human pancreatic cancer correlates with enhanced biological aggressiveness.
Immunohistochemical analysis of the p53 tumor suppressor gene was performed in 69 human pancreatic ductal adenocarcinomas, using a highly specific anti-p53 antibody. Nuclear immunoreactivity was found in 40 tumors, yielding an overall frequency of 58%. Immunoblotting confirmed that nuclear immunoreactivity was associated with increased p53 protein levels. p53 mRNA levels were increased in 9 of 9 tested cancers, without evidence for gene amplification. Analysis of the immunostaining data by chi-square and log-rank indicated that the presence of nuclear immunoreactivity correlated with a more advanced clinical stage, and a statistically significant decrease in the post-operative survival period. In 12 cancers, metastatic tissue samples were also available for p53 analysis. Nuclear p53 immunostaining in the primary tumors was not always associated with p53 immunoreactivity in the metastatic samples, and metastases occurred in the absence of nuclear p53 immunoreactivity in the primary lesion. These findings suggest that increased p53 protein levels in human pancreatic cancer may be due not only to p53 mutations which attenuate the degradation of the protein but also to an increase in p53 mRNA levels leading to increased p53 synthesis, and that p53 nuclear immunoreactivity in these cancers implies enhanced tumor aggressiveness but is not essential for the development of metastases.
Yokoyama
M
M
Department of Medicine, University of California, Irvine 92717.
Yamanaka
Y
Y
Friess
H
H
Buchler
M
M
Korc
M
M
D000918:Antibody Specificity; D015152:Blotting, Northern; D015139:Blotting, Southern; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D004273:DNA, Neoplasm / Q000032:analysis; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D010179:Pancreas / Q000166:cytology / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D015996:Survival Rate; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53