1Department of General Surgery, College of Medicine, Hanyang University. 2Department of Medical Genetics, College of Medicine, Hanyang University. 3Department of Pathology, College of Medicine, Sung Kyun Kwan University, Seoul, Korea.
ABSTRACT
PURPOSE: The role of mutation of p53 gene on the carcinigenesis was studied since 1991. There were some relationships of p53 mutation and clinicopathologic factors.
This sutudy was designed for the clinicopathologic and genetic factor relation in Korean breast cancer.
MATERIALS AND METHOD: A retrospective study on the clinicopathologic findings such as age, menopausal status, TNM stage, histologic grade, estrogen receptor, DNA ploidy and S-phase fraction was camed out on 47 breast cancer tissues which had been resected at the Department of Surgery, Hanyang University Hospital. Forty-seven tissues were grouped into 3 groups. Group 1 was ductal carcinoma in situ, Group 2 was invasive ductal carcinoma without axillary lymph node metastasis and Group 3 was invasive ductal carcinoma with axillary lymph node metastasis. The numbers of tissues in each groups were 14, 15 and 18, respectively.
Mutation screening on the p53 tumor suppressor gene was also performed with PCR-SSCP-direct sequencing method from the genomic DNA extracted from formalin fixed and paraffin-embedded pathologic tissue blocks. The results were as followings; RESULT: p53 mutations were detected in 12 cases(25.5%) of 47. In Group 1, 4 cases(28.6%) had mutations, and in Group 2, 5 cases(33.3%), and in Group3, 3 cases(16.7%). There was no significant differences in mutation rate between three groups. In 12 mutations detected, 6 cases were transition, 5 of which were missense mutation in coding sequences, and one of which was splicing mutation at acceptor site. One case was transversion and five cases were deletions or insertions of various lengths resulting in frameshift mutations. There was no statistically significant difference between groups and clinicopathologic factors except the strong relationship between the negative estrogen receptor and p53 mutation(p< 0.001).
CONCLUSIONS: From the above findings, p53 gene could be considered to be inactivated at the all stage of multistep carcinogenesis processes. The nature of mutations and genetic background of Korean breast cancers may be somewhat different from those of Caucasians. And the p53 mutation status may be used as one of the useful prognostic factors in addition to the estrogen receptor status.
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