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ISG15  is an ubiquitin-like molecule that is strongly upregulated by type I interferons as a primary response to diverse microbial and cellular stress stimuli. However, alterations in the  ISG15  signalling pathway have also been found in several human tumour entities. To the best of our knowledge, in the current study we present for the first time a systematic characterisation of  ISG15  expression in human breast cancer and normal breast tissue both at the mRNA and protein level.    Method  Using semiquantitative real-time PCR, cDNA dot-blot hybridisation and immunohistochemistry, we systematically analysed  ISG15  expression in invasive breast carcinomas ( n  = 910) and normal breast tissues ( n  = 135).  ISG15  protein expression was analysed in two independent cohorts on tissue microarrays; in an initial evaluation set of 179 breast carcinomas and 51 normal breast tissues; and in a second large validation set of 646 breast carcinomas and 10 normal breast tissues. In addition, a collection of benign and malignant mammary cell lines ( n  = 9) were investigated for  ISG15  expression.    Results   ISG15  was overexpressed in breast carcinoma cells compared with normal breast tissue, both at the RNA and protein level. Recurrence-free ( p  = 0.030), event-free ( p  = 0.001) and overall ( p  = 0.001) survival analyses showed a significant correlation between  ISG15  overexpression and unfavourable prognosis.    Conclusion  Therefore,  ISG15  may represent a novel breast tumour marker with prognostic significance and may be helpful in selecting patients for and predicting response to the treatment of human breast cancer.

The ubiquitin-like molecule interferon-stimulated gene 15 (ISG15) is a potential prognostic marker in human breast cancer