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p53 Mutations and Histological Type of Invasive Breast Carcinoma¹

Institute of Pathological Anatomy and Histology [A. M., F. B., S. P, D. C., D. C., M. B.], University of Pisa, Pisa, Italy; and Laboratory of Tumor Immunology and Biology, [F. D., R. C.], NIH, Bethesda, Maryland

² To whom request for reprints should be addressed, at Institute of Pathological Anatomy and Histology, University of Pisa, via Roma 57, 56100 Pisa, Italy.

A polymerase chain reaction-single strand conformation polymorphism assay 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 mucinous 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 p53 overex-pression using antibody PAb 1801. A specific immunostaining in 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 over-expression. However, in 9 cases having a mutated p53 gene we failed to find a positive immunoreaction. A significant association (P = 0.01) was present between mutations in the p53 gene and high proliferative activity of the tumors determined by immunohistochemistry with monoclonal antibody Ki-67. Moreover, a significantly higher expression of the Ki-67 antigen was found in medullary carcinomas compared to the other histotypes. Our findings indicate that in invasive breast carcinomas structural abnormalities of the p53 gene are mainly seen in medullary and ductal tumors and that the other histological types, especially those associated with a high level of differentiation and favorable prognosis, show a very low incidence of p53 mutations.

¹ This work was supported in part by Associazione Italiana per la Ricera sul Cancro (A.I.R.C.) and Consiglio Nazionale delle Ricerche (C.N.R.) Applicazioni Cliniche della Ricerca Oncologica (ACRO) No. 9202272.39.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 4/12/93. Accepted 7/29/93.

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