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 protein. 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 reinforce the notion that different germline mutations in TP53 may predispose to BC via different mechanisms.
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The authors declare that they have no conflict of interest.
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In all cases, patients underwent pre- and post-test genetic counseling and signed an informed consent for genetic testing. Information on mutation status and clinical data necessary for this study were obtained only after approval by the institutional ethics committees.
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Fitarelli-Kiehl, M., Giacomazzi, J., Santos-Silva, P. et al. The breast cancer immunophenotype of TP53-p.R337H carriers is different from that observed among other pathogenic TP53 mutation carriers. Familial Cancer 14, 333–336 (2015). https://doi.org/10.1007/s10689-015-9779-y
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DOI: https://doi.org/10.1007/s10689-015-9779-y