Abnormalities in the NF-kappaB Family and Related Proteins in Endometrial Carcinoma

J Pathol. 2004 Dec;204(5):569-77. doi: 10.1002/path.1666.

Abstract

The NF-kappaB family of transcription factors regulates a wide variety of cellular processes including cell growth, differentiation, and apoptosis. A tissue microarray was constructed from paraffin wax-embedded blocks from 95 endometrial carcinomas (EC), previously studied for microsatellite instability, as well as for alterations in PTEN, k-RAS and beta-catenin. Immunohistochemical evaluation included members of the NF-kappaB (p50, p65, p52, c-Rel, Rel-B) and the IkappaB (IkappaBalpha, IkappaBbeta, IkappaBepsilon, Bcl-3) families, as well as putative targets of NF-kappaB such as Flip, Bcl-xL, Cyclin D1, and oestrogen and progesterone receptors. Results were correlated with the clinical and pathological data. Nuclear immunostaining for members of the NF-kappaB family was frequent in EC (p50, 20%; p65, 16.5-21.9%; p52, 9.3%; c-Rel, 48.9%; Rel-B, 15.7%); and it correlated with negativity for members of the IkappaB family in some cases. There was a statistically significant association between immunoreaction for p50 and p65 (p = 0.006), suggesting activation of the so-called 'classic form' of NF-kappaB, similar to that described in breast cancer. Bcl-3 nuclear immunostaining was detected in 60.7% of cases. The vast majority of p52-positive tumours showed Bcl-3 nuclear immunoreaction (p = 0.038). Immunostaining for putative targets of NF-kappaB was as follows: Bcl-xL, 76.2% (p = 0.001); Flip 43.0%; Cyclin D1, 64.79%. p65 immunostaining correlated with increased immunoreaction for steroid hormone receptors. No correlation was found between NF-kappaB nuclear pattern and the presence of microsatellite instability, or alterations in PTEN, k-RAS, or beta-catenin. These results suggest that the NF-kappaB and IkappaB families of genes may be important in endometrial carcinogenesis, by controlling apoptosis and cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Antibodies, Neoplasm / immunology
  • Cytoplasm / genetics
  • Cytoplasm / pathology
  • Cytoskeletal Proteins / genetics
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / immunology
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, ras / genetics
  • Humans
  • I-kappa B Proteins / analysis
  • I-kappa B Proteins / genetics
  • Immunohistochemistry / methods
  • Microsatellite Repeats / genetics
  • NF-kappa B / analysis
  • NF-kappa B / genetics*
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / genetics*
  • Neoplasm Staging
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / genetics
  • Receptors, Estrogen / analysis
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / immunology
  • Receptors, Progesterone / analysis
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / immunology
  • Tissue Array Analysis / methods
  • Trans-Activators / genetics
  • Tumor Suppressor Proteins / genetics
  • beta Catenin

Substances

  • Antibodies, Neoplasm
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • I-kappa B Proteins
  • NF-kappa B
  • Neoplasm Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Trans-Activators
  • Tumor Suppressor Proteins
  • beta Catenin
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human