P53 MUTATIONS AND HISTOLOGICAL TYPE OF INVASIVE BREAST-CARCINOMA

A polymerase chain reaction-single strand conformation polymorphism as say was used to assess p53 mutations in 148 invasive breast carcinomas , selected on the basis of their histotype. They comprised 56 lobular, 47 ductal, 19 mucinous, 18 medullary, and 8 papillary carcinomas. The distribution of p53 mutations was significantly different (P = 0.006) in the histotypes examined: mutations were frequent in medullary (39% ) and ductal (26%), less common in lobular (12%), and absent in mucino us and papillary carcinomas. The frequency of mutations in the exon 5 of the p53 gene was significantly higher in medullary carcinomas than in the other histotypes: 5 (63%) of the mutations found in exon 5 were observed in medullary carcinomas (P = 0.012). One hundred twenty-two tumors from the total were also examined by immunohistochemistry for p 53 overexpression using antibody PAb 1801. A specific immunostaining i n neoplastic cells was present in 12 tumors. A strong correlation (P < 0.001) was observed between p53 mutations and nuclear accumulation of the p53 protein: 10 tumors were scored positive for both p53 mutation and overexpression. However, in 9 cases having a mutated p53 gene we failed to rind a positive immunoreaction. A significant association (P = 0.01) was present between mutations in the p53 gene and high prolif erative activity of the tumors determined by immunohistochemistry with monoclonal antibody Ki-67. Moreover, a significantly higher expressio n of the Ki-67 antigen was found in medullary carcinomas compared to t he other histotypes. Our findings indicate that in invasive breast car cinomas structural abnormalities of the p53 gene are mainly seen in me dullary and ductal tumors and that the other histological types, espec ially those associated with a high level of differentiation and favora ble prognosis, show a very low incidence of p53 mutations.