Nuclear Factor-κB signature of feline injection site sarcoma by immunohistochemistry

Introduction: The nuclear factor-kB (NF-kB) transcription factors consist of dimeric proteins of the Rel homology family known to be involved in inflammatory and stress responses. Inappropriate NF-kB activation can stimulate cell transformation and growth. In addition,NF-kB seems to have a role in tumours with a high inflammatory component. The NF-kB protein family is composed of different members: p50, p52, p65, cRel and RelB, which form homodimers and heterodimers. Only specific combinations ofNF-kB family members are transcriptionally active. The aim of this study was to evaluate immunohistochemically the expression of the different NF-kB transcription members in feline injection site sarcoma(FISS) (with inflammatory component) and in spontaneous feline soft tissue fibrosarcoma (FSTF) (without inflammatory component) in order to compare the presence of transscriptionally active NF-kB dimers between the two tumours. Materials andMethods: Twenty-three cases of FISS and eleven cases of FSTF were analysed by immunohistochemistry to determine expression of p65, p50, p52 and RelB. Labelling was evaluated semiquantitatively for percentage and intensity. The score for each antibody represented the product of percentage of positive tumour cells and intensity. Scores from 1e3 were considered as low expression and without functional activity, scores from 4e6 as intermediate expression and scores 7 as high expression. For each case we looked for transcriptionally active combinations of NF-kB family, taking into account the fact that homodimers of p50 or p52 or the heterodimer p50/p52 are transcriptionally inactive. When transcriptionally active NF-kB dimers were identified the tumour was considered positive for NF-kB. Results: Twenty of 23 (87%) FISS specimens had transcriptionally active NF-kB dimers and two (18%) FSTF specimens had transcriptionally active NF-kB. Conclusions: NF-kB is more often activated in FISS compared with FSTF. The NF-kB transcription factor pathway may be important in cancer-related inflammation and represents a phenotypic signature of FISS and possibly offers a novel molecular target for treatment of FISS