Abstract. We have attempted to determine the incidence, nature and clinical significance of TP53 mutation in a group of white (242 cases) and African-Brazilian (52 cases) patients with breast cancer. The interethnic admixture as estimated by STR markers showed that white subjects displayed 67.9±0.4%, 25.0±1.7% and 7.0%±1.6% and the black populations had 34.4±1.9%, 56.2±1.9 and 9.4±2.2% respectively of European, African and Amerindian genes. Clinical parameters such as age, lymph node status and steroid receptors were similar in both groups. African-Brazilian patients presented more advanced lesions. Mutation screening was performed using polymerase chain reaction-single strand conformation analysis followed by sequencing. Compared to whites (13.6%), a relatively high frequency of TP53 mutation was found in blacks (32.7%) (p=0.001). African-Brazilian women have a larger proportion of mutations in exons 5 and 7, whereas white women have more mutations in exon 8. Mutations within exon 4 were found only in tumors of white patients. The spectra of TP53 mutations show that A:T➝G:C nucleotide transversion and G:C➝C:G transition were more common in African-Brazilian women whereas G:C➝T:A transversion occurs very frequently in whites. A high prevalence of G:C➝A:T nucleotide transitions and deletions was detected in both groups. No association was found between p53 gene mutation and tumor or clinical parameters independently of the ethnic group. With a median follow-up of 35.6 months for whites and 43.4 months for the blacks, no differences in overall survival were found. If white patients were stratified according to the type and location of TP53 mutations, patients with mutations affecting amino acids directly involved in DNA or Zn binding displayed a poor prognosis. The pattern of mutations found in our population seems to reflect a base line pattern observed in populations with similar ethnic profile with some modifications, which might be derived from specific etiological factors. Introduction The tumor suppressor gene TP53 is a transcription factor that is implicated in the regulation of several biological pathways, such as cell growth, gene transcription, apoptosis, senescence and genomic stability (1). The biological activities of p53, especially in the regulation of DNA repair and apoptosis make it a potential prognostic and predictive marker. In addition, it is a useful end point marker in human cancer epidemiology. The patterns of TP53 mutations might reflect the effects of chronic carcinogen exposure in populations with different geographical and ethnic backgrounds (2,3). TP53 mutations have been associated with the tumorigenic process in the majority of human cancers (4). Of the TP53 mutations 80-90% involve exons 5 to 8 spanning the evolutionary conserved region of the protein (domains II to V). However, the nature, type and site of these mutations vary among different tumor types and depend on different carcinogen exposure (5). Breast cancer is the most frequent fatal cancer in women, presenting a variable and unpredictable course of disease. Several groups have investigated the occurrence of TP53 mutations in breast cancer. The frequency of these TP53 mutations varies considerably ranging from 12 to 60% (6). An increasing number of studies have attempted to analyse the value of p53 mutational status in prognostic evaluation (7-10). INTERNATIONAL JOURNAL OF ONCOLOGY 23: 189-196, 2003 189 TP53 mutations in primary breast carcinomas from white and African-Brazilian patients MARIA APARECIDA NAGAI 1 , HELENEMARIE SCHAER BARBOSA 2 , MARCO ANTONIO ZAGO 3 , WILSON ARAÚJO SILVA Jr 3 , INÊS NOBUKO NISHIMOTO 4 , SIBELI SALAORNI 1 , LÍVIA NERY FRANCO GUERREIRO COSTA 2 , MARCOS SILVA ARAÚJO 2 , ANA GABRIELA CALDAS OLIVEIRA 4 , MÁRIO MOURÃO NETO 4 and MARIA MITZI BRENTANI 1 1 Departamento de Radiologia, Disciplina de Oncologia da Faculdade de Medicina da Universidade de São Paulo, Av. Dr Arnaldo 455, 4˚ andar, Sala 4112, 01246.903, São Paulo, SP; 2 Departamento de Anatomia Patológica, LBCC-Hospital Aristides Maltez, Av. Dom João VI 322, 409.285-001, Brotas, Salvador, BA; 3 Fundação Hemocentro de Ribeirão Preto, Rua Tenente Catão Roxo, 2.501, Campos Universitário, 144.051-140, Ribeirão Preto; 4 Fundação Antônio Prudente, Rua Professor Antonio Prudente 211, 01509-900, São Paulo, Brasil Received October 14, 2002; Accepted January 9, 2003 _________________________________________ Correspondence to: Dr Maria Mitzi Brentani, Disciplina de Oncologia, Departamento de Radiologia da Faculdade de Medicina da Universidade de São Paulo, Av. Dr Arnaldo 455, 4˚ andar, Sala 4112, CEP-01296-903, São Paulo, Brazil E-mail: mbrentani@lim24.fm.usp.br Key words: breast cancer, TP53, mutations, race