Somatic mutation of the p53 gene is a very frequent event in the development of human neoplasms. Many of the mutations in p53 found in human tumors are point mutations and mutant proteins are much more stable than the normal protein and accumulates to...
Somatic mutation of the p53 gene is a very frequent event in the development of human neoplasms. Many of the mutations in p53 found in human tumors are point mutations and mutant proteins are much more stable than the normal protein and accumulates to a high level which permits important information about p53 expression to be obtained by immunohistochemical stainings.
It has been described that a new proto-oncogene, the murine double-minute 2(MDM2), becomes oncogenic due to amplification and overexpression. MDM2 protein can associate with both mutant and wild type p53 tumor suppressor gene products and thus inhibit p53-mediated transactivation of other genes. Immunohistochemical studies investigating the quantity of MDM2 protein in human sarcomas revealed an overexpression in 30% of the specimens. The author had performed an immunohistochemical staining with antibodies against to p53 protein, MDM2 protein, and NM23 protein which is a recently described as an antimetastatic gene product(nucleoside diphosphate kinase) in paraffin-embedded tissue from breast cancers biopsies. Results obtained were as followings;
1. On the normal breast tissue, p53 protein showed no reaction on the duct epithelia and myoepithelial cells. MDM2 protein showed nuclear and cytoplasmic expression of the duct epithelia and the myoepithelial cells. And NM23 protein showed nuclear and cytoplasmic expression of the duct epithelia and no reaction on the myoepithelial cells.
2. On the tumor cells of intraductal carcinomas, p53 showed no expression, and 12 cases among 51 cases(24.5%) of the infiltrating ductal carcinomas showed nuclear overexpression of the p53.
3. Depending upon the regional nodal metastases, there are 4 cases of expression of the p53 among 15 cases without nodal involvement and 7 cases of overexpression of p53 among the 29 cases with nodal involvement.
4. Expressions of the MDM2 and NM23 were variable; mostly nuclear and cytoplasmic positive reactions and one case of no expression, respectively. Immunohistochemical expression of the MDM2 and NM23 can not be helpful to detect the amplification of the gene.
The above results suggest the possible role of p53 mutation and MDM2 proteins in the carcinogenesis of the human breast cancers, but no correlationship between immunohistochemical expression of NM23 protein and the nodal metastasis of the breast cancers.