Overexpression of HRad17 mRNA in human breast cancer: correlation with lymph node metastasis

Clin Cancer Res. 2001 Sep;7(9):2815-20.

Abstract

Purpose: A novel human gene, designated HRad17, was identified as the human homologue of the Rad17 of Schizosaccharomyces pombe and Rad24 of Saccharomyces cerevisiae. In yeast, these genes play a critical role in maintaining genomic stability. The aim of this study was to evaluate the expression of HRad17 in human breast cancer.

Experimental design: We investigated HRad17 mRNA expression in 64 cases of human breast cancer by means of reverse-transcription-PCR, in situ hybridization, and immunohistochemistry.

Results: The HRad17 mRNA was overexpressed in 35 cases (54.7%). Twenty-four (68.6%) of 35 cases with HRad17 overexpression in cancer tissues were node-positive, whereas only 8 (27.6%) of 29 cases without HRad17 overexpressions were node-positive. The expression of HRad17 mRNA correlated with both lymph node metastasis (P = 0.001) and high Ki67 labeling index (P = 0.006). Although not significantly different, expression of HRad17 mRNA tended to correlate with tumor size (P = 0.06) and expression of mutant p53 protein (P = 0.10). Furthermore, expression of HRad17 mRNA was an independent predictor of axillary lymph node metastasis as well as of lymphatic permeation by multivariate analysis (P < 0.0001).

Conclusions: Our study demonstrates that HRad17 might be related to the development of lymph node metastasis in human breast cancers. Although its function still remains unclear, the expression of HRad17 mRNA could open up a new window for the diagnostic staging and treatment of human breast cancers.

MeSH terms

  • Adult
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Ki-67 Antigen / analysis
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Middle Aged
  • Multivariate Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Cell Cycle Proteins
  • Ki-67 Antigen
  • RNA, Messenger
  • Rad17 protein, human
  • Tumor Suppressor Protein p53