Abnormalities in the NF-kappaB family and related proteins in endometrial carcinoma.
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.
Department of Pathology and Molecular Genetics, Departament de Ciències Mèdiques Bàsiques, University of Lleida, Hospital Universitari Arnau de Vilanova, Av. Alcalde Rovira Roure 80, 25108 Lleida, Spain.
Judit
J
Pallares
Jose Luis
JL
Martínez-Guitarte
Xavier
X
Dolcet
David
D
Llobet
Montserrat
M
Rue
José
J
Palacios
Jaime
J
Prat
Xavier
X
Matias-Guiu
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000912:Antibodies, Neoplasm / Q000276:immunology; D003593:Cytoplasm / Q000235:genetics / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D020672:I-kappa B Proteins / Q000032:analysis / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D018895:Microsatellite Repeats / Q000235:genetics; D016328:NF-kappa B / Q000032:analysis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics / Q000276:immunology; D011980:Receptors, Progesterone / Q000032:analysis / Q000235:genetics / Q000276:immunology; D046888:Tissue Array Analysis / Q000379:methods; D015534:Trans-Activators / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D051176:beta Catenin
D000912:Antibodies, Neoplasm; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human