title: The breast cancer immunophenotype of TP53-p.R337H carriers is different from that observed among other pathogenic TP53 mutation carriers.
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.
authors.affiliation: Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil, marianakiehl@gmail.com.
authors.forename: Mariana
authors.initials: M
authors.lastname: Fitarelli-Kiehl
authors.forename: Juliana
authors.initials: J
authors.lastname: Giacomazzi
authors.forename: Patricia
authors.initials: P
authors.lastname: Santos-Silva
authors.forename: Marcia Silveira
authors.initials: MS
authors.lastname: Graudenz
authors.forename: Edenir Inez
authors.initials: EI
authors.lastname: Palmero
authors.forename: Rodrigo Augusto Depieri
authors.initials: RA
authors.lastname: Michelli
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Achatz
authors.forename: Cynthia Aparecida Bueno
authors.initials: CA
authors.lastname: de Toledo Osório
authors.forename: Victor Evangelista
authors.initials: VE
authors.lastname: de Faria Ferraz
authors.forename: Clarissa Gondim
authors.initials: CG
authors.lastname: Picanço
authors.forename: Patricia
authors.initials: P
authors.lastname: Ashton-Prolla
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012189:Retrospective Studies
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human