Abnormalities in the NF-κB family and related proteins in endometrial carcinoma

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 betacatenin. 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%; cRel, 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, kRAS, 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