Loss of hMSH2 expression in primary breast cancer with p53 alterations

Ilaria Spagnoletti, Claudia Pizzi, Annamaria Galietta, Massimo Di Maio, Paolo Mastranzo, Santa Daniele, Gennaro Limite, Guido Pettinato, Alma Contegiacomo

Research output: Contribution to journalArticle

Abstract

Inactivation of DNA mismatch repair genes (MRG) is a recently described pathway of cancer development and progression resulting in genetic instability. Germline mutations in MRG have been studied predominantly in patients with hereditary non-polyposis colorectal cancer (HNPCC) where it is associated with microsatellite instability (MSI). The expression of MRG in primary breast cancer is still largely unexplored. The hMSH2 MRG encodes a protein that recognizes and binds to mismatch sequences of DNA. We investigated the relationship between hMSH2 expression and clinicopathological and biological characteristics, including p53 and pl85 expression, in 44 primary invasive breast cancers. hMSH2 was not expressed in 11 cases (25%). Interestingly, p53 (p=0.05), pl85 and steroidal receptor expression (p=0.07) were more frequent in tumors without hMSH2 expression. Furthermore, in 30 of 44 cases we analyzed hMSH2 expression in relation to MSI at 9 dinucleotide loci, and found that MRG expression was not significantly related to MSI. The presence of hMSH2 and p53 alterations in the same tumor suggests that the two oncoproteins act through a common mutational pathway, whereas the absence of a correlation between hMSH2 and MSI suggests that oncogenetic mechanisms of progression in primary breast cancer differ from those in HNPCC.

Original languageEnglish
Pages (from-to)845-851
Number of pages7
JournalOncology Reports
Volume11
Issue number4
Publication statusPublished - Apr 2004

Keywords

  • Breast cancer
  • hMSH2
  • Microsatellite instability
  • p185
  • p53

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Spagnoletti, I., Pizzi, C., Galietta, A., Di Maio, M., Mastranzo, P., Daniele, S., Limite, G., Pettinato, G., & Contegiacomo, A. (2004). Loss of hMSH2 expression in primary breast cancer with p53 alterations. Oncology Reports, 11(4), 845-851.