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A TP53 founder mutation, p.R337H, is associated with phyllodes breast tumors in Brazil

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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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Authors and Affiliations

  1. Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, 90035-903, Porto Alegre, RS, Brazil

    Juliana Giacomazzi, Patricia Koehler-Santos, Mariana Fitarelli-Kiehl & Patricia Ashton-Prolla

  2. Post-Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil

    Juliana Giacomazzi & Patricia Ashton-Prolla

  3. Protein and Molecular Analysis Laboratory, Experimental Research Center, HCPA, Porto Alegre, Brazil

    Patricia Koehler-Santos

  4. Molecular Oncology Research Center, Hospital do Câncer de Barretos, Barretos, Brazil

    Edenir Inez Palmero, Rodrigo Depieri Michelli & Cristovam Scapulatempo Neto

  5. Pathology Service, HCPA, Porto Alegre, Brazil

    Marcia S. Graudenz, Luis Fernando Rivero & Antonio Carlos Kruel Pütten

  6. Instituto de Patologia, Porto Alegre, Brazil

    Marcia S. Graudenz & Luis Fernando Rivero

  7. Pathology Service, Hospital Conceição, Porto Alegre, Brazil

    Eduardo Lima

  8. International Prevention Research Institute, Lyon, France

    Pierre Hainaut

  9. Department of Statistics, Institute of Mathematics, UFRGS, Porto Alegre, Brazil

    Suzi Alves Camey

  10. Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil

    Mariana Fitarelli-Kiehl & Patricia Ashton-Prolla

  11. Laboratório Geyer, Porto Alegre, Brazil

    Geraldo Geyer

  12. Laboratório Medicina Digital, Porto Alegre, Brazil

    Luise Meurer

  13. Laboratório Patologistas Reunidos, Porto Alegre, Brazil

    Ana Geiger

  14. Laboratório ANATPAT, Porto Alegre, Brazil

    Monica Blaya Azevedo

  15. Pathology Service, Hospital São Lucas da Pontíficia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil

    Vinicius Duval da Silva

  16. Medical Genetics Service, HCPA, Porto Alegre, Brazil

    Patricia Ashton-Prolla

Authors
  1. Juliana Giacomazzi
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  2. Patricia Koehler-Santos
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  3. Edenir Inez Palmero
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  4. Marcia S. Graudenz
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  5. Luis Fernando Rivero
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  6. Eduardo Lima
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  7. Antonio Carlos Kruel Pütten
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  8. Pierre Hainaut
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  9. Suzi Alves Camey
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  10. Rodrigo Depieri Michelli
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  11. Cristovam Scapulatempo Neto
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  12. Mariana Fitarelli-Kiehl
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  13. Geraldo Geyer
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  14. Luise Meurer
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  15. Ana Geiger
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  16. Monica Blaya Azevedo
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  17. Vinicius Duval da Silva
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  18. Patricia Ashton-Prolla
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Correspondence to Juliana Giacomazzi.

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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

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