SHORT COMMUNICATION The breast cancer immunophenotype of TP53-p.R337H carriers is different from that observed among other pathogenic TP53 mutation carriers Mariana Fitarelli-Kiehl • Juliana Giacomazzi • Patricia Santos-Silva • Marcia Silveira Graudenz • Edenir Inez Palmero • Rodrigo Augusto Depieri Michelli • Maria Isabel Achatz • Cynthia Aparecida Bueno de Toledo Oso ´rio • Victor Evangelista de Faria Ferraz • Clarissa Gondim Picanc ¸o • Patricia Ashton-Prolla Ó Springer Science+Business Media Dordrecht 2015 Abstract Germline TP53 mutations are associated with Li–Fraumeni syndrome, an autosomal dominant disorder characterized by a predisposition to multiple early-onset cancers including breast cancer (BC), the most prevalent tumor among women. The majority of germline TP53 mutations are clustered within the DNA-binding domain of the gene, disrupting the structure and function of the pro- tein. A specific germline mutation in the tetramerization domain of p53, p.R337H, was reported at a high frequency in Southern and Southeastern Brazil. This mutation appears to result in a more subtle defect in the protein, which becomes functionally deficient only under particular conditions. Recent studies show that the BC phenotype in TP53 mutation carriers is often HER2 positive (63–83 %). Considering that the immunophenotype of BC among p.R337H carriers has not been reported, we reviewed immunohistochemistry data of 66 p.R337H carriers in comparison with 12 patients with other non-functional TP53 germline mutation. Although 75 % of carriers of these mutations showed significant HER2 overexpression (3?), corroborating previous studies, only 22.7 % of p.R337H patients had BC overexpressing HER2. These results rein- force the notion that different germline mutations in TP53 may predispose to BC via different mechanisms. M. Fitarelli-Kiehl Á P. Ashton-Prolla Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil M. Fitarelli-Kiehl (&) Á P. Santos-Silva Á P. Ashton-Prolla Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clı ´nicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, Rio Grande do Sul 90035-903, Brazil e-mail: marianakiehl@gmail.com J. Giacomazzi Á P. Ashton-Prolla Department of Genetics, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil P. Santos-Silva Á P. Ashton-Prolla Post-Graduate Program in Medicine, Medical Sciences, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil M. S. Graudenz Department of Pathology, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil M. S. Graudenz Instituto de Patologia, Porto Alegre, Rio Grande do Sul, Brazil E. I. Palmero Á R. A. D. Michelli Molecular Oncology Research Center, Hospital de Ca ˆncer de Barretos, Barretos, Sa ˜o Paulo, Brazil M. I. Achatz Department of Oncogenetics, International Research Center, Hospital do Ca ˆncer A.C. Camargo (HCACC), Sa ˜o Paulo, Sa ˜o Paulo, Brazil C. A. B. de Toledo Oso ´rio Pathology Service, HCACC, Sa ˜o Paulo, Sa ˜o Paulo, Brazil V. E. de Faria Ferraz Á C. G. Picanc ¸o Department of Genetics, Faculdade de Medicina de Ribeira ˜o Preto, Universidade de Sa ˜o Paulo (FMRP-USP), Ribeira ˜o Preto, Sa ˜o Paulo, Brazil V. E. de Faria Ferraz Center for Medical Genomics, Hospital das Clı ´nicas da Faculdade de Medicina de Ribeira ˜o Preto, Universidade de Sa ˜o Paulo (HCFMRP-USP), Ribeira ˜o Preto, Sa ˜o Paulo, Brazil 123 Familial Cancer DOI 10.1007/s10689-015-9779-y