Clinical Observations
p53 MUTATIONS AND PROTEIN OVEREXPRESSION IN PRIMARY COLORECTAL CANCER AND ITS LIVER METASTASIS
Abstract
Objective: To compare p53 status in primary and hepatic metastatic colorectal cancer in 34 patients.
Methods: p53 gene status (exons 5-9) was examined by PCR, denaturing gradient gel electrophoresis (DGGE) and automated sequencing. P53 protein was detected by immunohistochemistry using monoclonal antibody DO-7.
Results: p53 mutations were found in exons 5 through 9 in 21 of 34 patients (61.8%). Among them, 5 patients had mutation in liver metastasis but not in their primary tumors while in the other patients the same mutations were found in both primary and metastatic colorectai cancers. In no patients was p53 mutation exclusively found in the primary colorectal tumors. Moreover, additional mutation was detected in the metastatic lesions in two cases. Of the 37 mutations within the exons examined, 73% was misseuse mutation and 16% was nonsense mutation. There were 4 microinsertions, p53 protein was overexpressed in both primary and metastatic colorectai cancers with p53 gene mutations. The presence of p53 mutation significantly correlated with p53 protein accumulation (r=0.96, P< 0.001). However, in 4 patients with p53 nonsense mutation, immunohistochemical staining was negative. In three patients who showed no p53 mutation of the primary tumor, p53 protein was consistently overexpressed.
Conclusion: In colorectal cancers, p53 gene mutation usually appears first in the primary tumor and maintains as such but is more prominent when metastasized to the liver. However, p53 gene mutation may occur only after being metastasized. Although p53 gene mutation and p53 protein overexpression correlate with each other, either parameter examined alone may lead to false positive or negative results.
Methods: p53 gene status (exons 5-9) was examined by PCR, denaturing gradient gel electrophoresis (DGGE) and automated sequencing. P53 protein was detected by immunohistochemistry using monoclonal antibody DO-7.
Results: p53 mutations were found in exons 5 through 9 in 21 of 34 patients (61.8%). Among them, 5 patients had mutation in liver metastasis but not in their primary tumors while in the other patients the same mutations were found in both primary and metastatic colorectai cancers. In no patients was p53 mutation exclusively found in the primary colorectal tumors. Moreover, additional mutation was detected in the metastatic lesions in two cases. Of the 37 mutations within the exons examined, 73% was misseuse mutation and 16% was nonsense mutation. There were 4 microinsertions, p53 protein was overexpressed in both primary and metastatic colorectai cancers with p53 gene mutations. The presence of p53 mutation significantly correlated with p53 protein accumulation (r=0.96, P< 0.001). However, in 4 patients with p53 nonsense mutation, immunohistochemical staining was negative. In three patients who showed no p53 mutation of the primary tumor, p53 protein was consistently overexpressed.
Conclusion: In colorectal cancers, p53 gene mutation usually appears first in the primary tumor and maintains as such but is more prominent when metastasized to the liver. However, p53 gene mutation may occur only after being metastasized. Although p53 gene mutation and p53 protein overexpression correlate with each other, either parameter examined alone may lead to false positive or negative results.
