P53 GENE ALTERATIONS IN SPECIAL TYPES OF BREAST-CARCINOMA - A MOLECULAR AND IMMUNOHISTOCHEMICAL STUDY IN ARCHIVAL MATERIAL

The p53 locus on the short arm of chromosome 17 at 17p13.1 was examine d for small genomic deletions and mutations in 23 formalin-fixed, para ffin-embedded cases of special types of breast carcinoma (six medullar y, seven apocrine, five differentiated tubular, and five papillary). p 53 mutations in the evolutionarily conserved exons 5-9 were detected i n 11 cases (four apocrine, two papillary, two medullary, and three dif ferentiated tubular), using the novel non-radioactive PCR-based Hydrol ink mutation detection enhancement (MDE) method, and confirmed by dire ct sequencing of the PCR products. Missense mutations causing amino ac id substitutions were evenly distributed among exons. One case of apoc rine carcinoma showed a polymorphism at codon 213 (CGA-->CGG). Twelve out of 23 cases were found to express a strong nuclear signal against CM-1 and DO-7, two anti-p53-specific antibodies. Small genomic deletio ns in the vicinity of the p53 locus were detected in 11 tumours (three papillary, three differentiated tubular, two medullary, and three apo crine carcinomas), using the multiplex PCR method. No statistical corr elation was found between deletions at 17p13.1 and p53 mutations (P<0 . 5). In addition, p53 mutations and immunoexpression correlated with the c-erbB-2 gene product, an oncogenic protein that has been implicat ed in cell cycle control (P<0 . 001). Our findings suggest that genomi c alterations of the p53 gene are quite common events associated with special types of breast carcinoma, particularly of the apocrine subtyp e, but the prognostic value is unlikely to be of clinical importance.