In mismatch�\repair (MMR)�\proficient colorectal cancer, MUC1 expression and MUC2 loss are adverse prognostic selleckbio factors. In MLH1�\negative colorectal cancer, loss of MUC2 is associated with advanced N (node) stage and reduced survival. In MLH1�\negative colorectal cancer, MUC1 expression shows trends towards associations with a favourable outcome. This may be explained by the association between MUC1 and MUC2 expression in mucinous carcinomas, which are over�\represented in this subset. Acknowledgements This study was supported by a grant from the Swiss National Foundation (grant number PBBSB�\110417) and the Novartis Foundation, formerly Ciba�\Geigy�\Jubilee�\Foundation. We thank Privatdozent Dr Hanspeter Spichtin, Institute of Clinical Pathology, Basel, Switzerland, and Professor Robert Maurer, Institute of Pathology, Stadtspital Triemli, Zuerich, Switzerland for providing the cases.

Abbreviations CRC – colorectal cancer HNPCC – hereditary non�\polyposis colon cancer MMR – mismatch repair MUC – mucin MSI�\H – microsatellite instability�\high TMA – tissue microarray Footnotes Competing interests: None declared.
Interferons (IFNs) are central mediators of immune responses to viral infections (1). They exert their antiviral activity by inducing the expression of hundreds of genes that together establish an ��antiviral state,�� which restricts the spread of virus among neighboring cells (2). Type I IFNs (all IFN-��s and IFN-��) bind to the IFN-�� receptor (IFNAR) and activate the receptor-associated tyrosine kinases Jak1 and Tyk2, which in turn activate signal transducer and activator of transcription 1 (STAT1) and STAT2 by phosphorylation of a tyrosine in the C-terminal domain (3).

Activated STAT1 combines with STAT2 and IFN regulatory factor 9 (IRF9) to form IFN-stimulated gene factor 3 (ISGF3). ISGF3 translocates into the nucleus, binds to IFN-stimulated response elements (ISREs) in gene promoters and induces the transcription of hundreds of genes. Activated STAT1 can also form homodimers that bind to ��-activated sequences (GASs) and induce an overlapping but distinct set of IFN-stimulated genes (ISGs). IFN-induced Jak/STAT signaling is tightly controlled by negative regulators. Suppressor of cytokine signaling 1 (SOCS1) and SOCS3 are rapidly induced and strongly inhibit STAT1 phosphorylation at the receptor-kinase complex within hours (4).

SOCS proteins are also rapidly degraded and in most cells become undetectable within hours after their induction. However, IFN signaling remains refractory for days in many cell types (5). In the liver of mice repeatedly injected with IFN-��, a long-lasting upregulation of ubiquitin-specific peptidase 18 Carfilzomib (USP18) was found to be responsible for prolonged unresponsiveness of liver cells to IFN-�� (6). For more than 25 years, recombinant IFN-�� has been used for the treatment of hepatitis C virus (HCV) infections (7).