The breast cancer immunophenotype of TP53-p.R337H carriers is different from that observed among other pathogenic TP53 mutation carriers

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-...

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Bibliographic Details
Published in:Familial cancer 2015-06, Vol.14 (2), p.333-336
Main Authors: Fitarelli-Kiehl, Mariana, Giacomazzi, Juliana, Santos-Silva, Patricia, Graudenz, Marcia Silveira, Palmero, Edenir Inez, Michelli, Rodrigo Augusto Depieri, Achatz, Maria Isabel, de Toledo Osório, Cynthia Aparecida Bueno, de Faria Ferraz, Victor Evangelista, Picanço, Clarissa Gondim, Ashton-Prolla, Patricia
Format: Article
Language:English
Subjects:
Adult
Aged
Biomedical and Life Sciences
Biomedicine
Breast Neoplasms - etiology
Breast Neoplasms - genetics
Cancer Research
Epidemiology
Female
Genes, p53
Genetic Predisposition to Disease
Germ-Line Mutation
Heterozygote
Human Genetics
Humans
Immunophenotyping
Middle Aged
Receptor, ErbB-2 - analysis
Retrospective Studies
Short Communication
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Summary: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.
ISSN:1389-9600
1573-7292
DOI:10.1007/s10689-015-9779-y