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.
Pallares
Judit
J
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.
Martínez-Guitarte
Jose Luis
JL
Dolcet
Xavier
X
Llobet
David
D
Rue
Montserrat
M
Palacios
José
J
Prat
Jaime
J
Matias-Guiu
Xavier
X
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