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Abnormalities in the NF‐κB family and related proteins in endometrial carcinoma
Author(s) -
Pallares Judit,
MartínezGuitarte Jose Luis,
Dolcet Xavier,
Llobet David,
Rue Montserrat,
Palacios José,
Prat Jaime,
MatiasGuiu Xavier
Publication year - 2004
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1666
Subject(s) - immunostaining , biology , immunohistochemistry , cancer research , pten , cyclin d1 , p50 , progesterone receptor , pathology , cancer , transcription factor , medicine , apoptosis , breast cancer , estrogen receptor , cell cycle , pi3k/akt/mtor pathway , gene , immunology , genetics
The NF‐κB 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‐κB (p50, p65, p52, c‐Rel, Rel‐B) and the IκB (IκBα, IκBβ, IκBε, Bcl‐3) families, as well as putative targets of NF‐κB 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‐κB 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 IκB 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‐κB, 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‐κB 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‐κB nuclear pattern and the presence of microsatellite instability, or alterations in PTEN, k‐RAS, or beta‐catenin. These results suggest that the NF‐κB and IκB families of genes may be important in endometrial carcinogenesis, by controlling apoptosis and cell proliferation. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.