Abstract
A few studies have reported phyllodes tumors (PT) of the breast with germline TP53 mutations. Given this potential association and the high frequency of the TP53 p.R337H in southern and southeastern Brazil, the aim of this study was to assess whether p.R337H occurs among women diagnosed with such rare tumors in this region. Benign, borderline, and malignant breast PT were retrieved from eight pathology laboratories, and DNA was extracted from tumor tissue to perform p.R337H analysis. Overall, 128 cases classified as benign, 7 as borderline, and 13 as malignant PT were included in the study. The TP53 p.R337H mutation was identified in tumor cells of eight (5.4 %) cases. Analysis of DNA from non-tumoral tissue was possible in two of these, and both were p.R337H carriers in the germline. In addition, haplotype analysis was done in these two p.R337H carriers showing the presence of the founder haplotype previously reported in Brazilian mutation-positive individuals. Mutation frequency was significantly higher among malignant (3 of 13; 23 %) compared to benign tumors (5 of 128; 3.4 %) (p = 0.004). Mean age at PT diagnosis was not significantly different between mutation carriers and non-carriers. However, when subgroups where analyzed, the difference in age at diagnosis of carriers versus non-carriers within the group of benign tumors reached borderline significance. Our findings reinforce previous evidence that TP53 mutations have an important role in the development of both benign and malignant PT of the breast.
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Acknowledgments
The authors wish to thank Zeli Fogaça, Marta Recktenvald, Maria Teresinha Manuel, and Alexandre Marques Machado for laboratory support. The work of JG was supported by fellowships from CAPES and CNPQ (Brazil). Genotyping analyses were performed in the Experimental Research Center of Hospital de Clínicas de Porto Alegre, Brazil, and at the International Agency for Research in Cancer, Lyon, France. The study was supported in part by grants from GlaxoSmithKline Oncology (Ethnic Research Initiative Grant Award 2009), U.K.; CNPq to PA-P (grant 307779 2009-2), Brazil; FAPERGS-PPSUS (grant 09/0103-0), FAPERGS PRONEX (grant 10/0051-9), and Fundo de Incentivo a Pesquisa e Eventos, Hospital de Clínicas de Porto Alegre (GPPG 08080), Brazil.
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Giacomazzi, J., Koehler-Santos, P., Palmero, E.I. et al. A TP53 founder mutation, p.R337H, is associated with phyllodes breast tumors in Brazil. Virchows Arch 463, 17–22 (2013). https://doi.org/10.1007/s00428-013-1439-8
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DOI: https://doi.org/10.1007/s00428-013-1439-8