Summary Protein expression of the putative tumour-suppressor gene DCC on chromosome 18q was evaluated in a panel of 16 201. In addition, 9 out of 15 normal tissue specimens were mutated in codon 201. In two out of three cases with homozygous wild-type codons in peripheral blood lymphocyte (PBL) DNA, mutations were already observed in the tumour adjacent normal colonic mucosa. We conclude that DCC immunostaining should be introduced in the clinicopathological routine because of its strong correlation with the known prognostic markers 18q LOH and mutation of codon 201.Keywords: DCC; tumour-suppressor gene; loss of heterozygosity; colorectal cancer; immunohistochemistry; prognosis Genetic alterations in multistep colorectal tumorigenesis include loss of heterozygosity (LOH) of the putative tumour-suppressing DCC (deleted in colon carcinoma) gene on chromosome 18q21.1 Fearon et al, 1990;lacopetta et al, 1994 (Vogelstein et al, 1988). Recently, Jen et al (1995) have reported that the status of chromosome 18q has prognostic value for the clinical course and the survival of CRC patients giving patients with stage II cancer and 18q LOH a similar prognosis than patients with stage III cancer. Furthermore, 18q LOH correlates with an increased likelihood of distant metastasis (Kern et al, 1989) and is a strong predictive factor for deep muscle and lymphatic invasion (lino et al, 1994). In more than 90% of carcinomas with 18q allelic loss the deleted region includes the DCC locus . Reduced or missing mRNA expression was observed in more than 50% of CRC (Itoh et al, 1993) but a general mechanism for inactivation of the remaining allele has not yet been elucidated.The DCC gene encodes a neural cell adhesion-like transmembrane protein. Its extracellular region is composed of six immunoglobulin-like domains and four fibronectin-type III repeats. Functionally, the DCC gene product might control cell division and it might play a critical role in embryonic development

Objective: Randomized trials have shown that concomitant methotrexate (MTX) augments the effectiveness of tumour necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA), but its benefit in psoriatic arthritis (PsA) has not been demonstrated. The goal of this study was to examine whether the impact of concomitant MTX on therapeutic outcomes in patients with PsA was similar to its effects in RA. Methods: We used data from highly comparable and concurrent observational studies of patients with PsA (N = 1424) or RA (N = 3148) who initiated adalimumab therapy during routine clinical care. The 28-joint Disease Activity Score (DAS28) and patient-reported pain scores were evaluated in patients who received 24 months of continuous treatment with adalimumab monotherapy or adalimumab + MTX and in patients who initiated or stopped concomitant MTX during ongoing adalimumab therapy. Results: Twenty-four months of continuous treatment with adalimumab + MTX was superior to adalimumab monotherapy in RA patients, while no significant difference was observed in patients with PsA. RA patients who added MTX during the study showed significant individual improvements in DAS28 and pain scores at 6 months after the change in therapy, while those who removed MTX had slight increases in disease activity. In contrast, in patients with PsA, neither initiation nor removal of MTX during continuous adalimumab therapy had a significant effect on therapeutic outcomes. Conclusion: Addition of MTX to adalimumab confers further therapeutic benefit in patients with RA, but not in those with PsA, suggesting differences in MTX effects in these two patient populations.