High frequency of concomitant nm23-H1 and E-cadherin transcriptional inactivation in primary non-inheriting colorectal carcinomas

J Mol Med (Berl). 2003 Apr;81(4):256-63. doi: 10.1007/s00109-003-0420-4. Epub 2003 Apr 2.


This study evaluated the added significance of nm23-H1 to that of E-cadherin in determining metastatic proclivity in primary sporadic colorectal carcinomas (SCRCs). A clinical cohort of 52 SCRCs was examined for the significance of nm23-H1 and E-cadherin mRNA levels and E-cadherin protein expression levels into the progression of colorectal tumor invasion, determined by their relevance compared with conventional biological markers. A more than twofold decreased expression of nm23-H1 mRNA was reported in 28/52 (54%) of the carcinomas and was positively associated with the presence of nodal metastases and Astler-Coller stages B1 and B2 in 29% and 35% of the SCRCs, respectively. Reduced expression of E-cadherin mRNA was reported in 38.5% of the carcinomas and was similarly associated with stages Astler-Coller B1 and B2 in 27% of the SCRCs. Decreased E-cadherin immunohistochemical expression (grades II and III) was observed in 67% of the samples. E-cadherin mRNA and protein expression were significantly related to each other. The nm23-H1 (+)/E-cadherin (+) coexpression profile was observed in 31% and was significantly related to the absence of lymph node metastases in 31% and stages Astler-Coller B1 and B2 in 29% of the carcinomas examined. Furthermore, the nm23-H1 (-)/E-cadherin (+) coexpression profile was coupled to decreased E-cadherin immunohistochemical protein detection (grade II) in 21% of the cases examined. These findings suggest that impairment of nm23-H1 expression is an early event into the progression of colorectal metastasis that precedes E-cadherin transcriptional silencing in the majority of SCRCs examined. Nm23-H1 may therefore play an important role in suppressing the early steps of metastasis in sporadic cases of colorectal carcinomas.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Cadherins / biosynthesis*
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Carcinoma / metabolism*
  • Cohort Studies
  • Colorectal Neoplasms / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Models, Biological
  • Monomeric GTP-Binding Proteins / biosynthesis*
  • Monomeric GTP-Binding Proteins / genetics*
  • NM23 Nucleoside Diphosphate Kinases
  • Nucleoside-Diphosphate Kinase*
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sex Factors
  • Tissue Distribution
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics*
  • Transcriptional Activation*


  • Biomarkers
  • Cadherins
  • NM23 Nucleoside Diphosphate Kinases
  • RNA, Messenger
  • Transcription Factors
  • NME1 protein, human
  • Nucleoside-Diphosphate Kinase
  • Monomeric GTP-Binding Proteins