KISS1 is a metastasis suppressor lost in several solid malignancies. We evaluated the clinical relevance of KiSS-1 methylation and its protein expression in colorectal cancer. The epigenetic silencing of KiSS-1 by hypermethylation was tested in colon cancer cells (n = 5) before and after azacytidine treatment. KiSS-1 methylation was evaluated by methylation-specific PCR in colorectal cancer cells, and normal, benign, and tumor tissues (n = 352) were grouped in a training set (n = 62) and two independent validation cohorts (n = 100 and n = 190). KiSS-1 protein expression was analyzed by immunohistochemistry on tissue arrays. KiSS-1 hypermethylation correlated with transcript and protein expression loss, being increased in vitro by azacytidine. Methylation rates were 53.1, 70.0, and 80.0 % in the training and validation sets, respectively. In the training set, KiSS-1 methylation rendered a diagnostic accuracy of 72.7 % (p = 0.002). Combination of KiSS-1 methylation and serum CEA (p = 0.001) increased the prognostic utility of CEA alone (p = 0.022). In the first validation set, KiSS-1 methylation correlated with tumor grade (p = 0.011), predicted recurrence (p = 0.009), metastasis (p = 0.004), disease-free (p = 0.034), and overall survival (p = 0.015). In the second validation cohort, KiSS-1 methylation predicted disease-specific survival (p = 0.030). In the training set, cytoplasmic KiSS-1 expression was significantly higher in nonneoplastic biopsies as compared to colorectal tumors (p < 0.0005). In the validation set, loss of cytoplasmic expression correlated with tumor stage (p = 0.007), grade (p = 0.035), recurrence (p = 0.017), and disease-specific survival (p = 0.022). KiSS-1 was revealed epigenetically modified in colorectal cancer. The diagnostic and prognostic utility of KiSS-1 methylation and expression patterns suggests their assessment for the clinical management of colorectal cancer patients.

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The objective of the present study was to determine the efficacy of anti-cyclic citrullinated peptide (anti-CCP) antibody detection in the early diagnosis of rheumatoid arthritis (RA), as well as to compare three commercially available enzyme-linked immunosorbent assay (ELISA) kits used to detect such antibodies. We analysed the presence of anti-CCP antibodies in the sera of 78 patients who had been newly referred from primary healthcare centres to the Early Polyarthritis Unit. We also included in the study a group of 50 healthy controls. None of the patients had previously received treatment for the disease. After 1-year follow-up, the diagnosis of RA was confirmed in 53 of these patients. The ELISA kits under study were IMMUNOSCAN RA (Euro-Diagnostica AB), QUANTA Lite CCP IgG ELISA (INOVA Diagnostic) and DIA-STAT Anti-CCP (Axis-Shield Diagnostics); the sensitivity obtained was 52.8%, 58.5% and 52.8%, respectively, with 100% specificity for all three kits. Anti-CCP antibodies detected the presence of RA in 26% of patients without positive rheumatoid factor (RF). The sum of anti-CCP antibodies or the presence of RF gave a sensitivity of up to 67%, with specificity ranging between 94 and 97%. Anti-CCP antibodies show high specificity for the diagnosis of RA. The three ELISAs analysed offer the same degree of diagnostic accuracy.

Erosive damage at 1 year in patients with recent-onset RA is significantly influenced by SE homozygosity and the presence of baseline erosions, but not by RF status, anti-CCP status, or -308 TNF-alpha genotype.

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