EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer

BACKGROUND: Proteolytic enzymes and their regulators have important biological roles in colorectal cancer by stimulating invasion and metastasis, which makes these factors attractive as potential prognostic biomarkers. METHODS: The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) was characterised using immunohistochemistry in primary tumours from a cohort of 277 prospectively recruited colorectal cancer patients, and associations with expression of S100A4, clinicopathological parameters and patient outcome were investigated. RESULTS: One hundred and ninety-eight samples (72%) displayed positive membrane staining of the tumour cells, whereas 10 cases (4%) were borderline positive. EMMPRIN expression was associated with shorter metastasis-free, disease-specific and overall survival in both univariate and multivariate analyses. The prognostic impact was largely confined to TNM stage III, and EMMPRIN-negative stage III patients had an excellent prognosis. Furthermore, EMMPRIN was significantly associated with expression of S100A4, and the combined expression of these biomarkers conferred an even poorer prognosis. However, there was no evidence of direct regulation between the two proteins in the colorectal cancer cell lines HCT116 and SW620 in siRNA knockdown experiments. CONCLUSION: EMMPRIN is a promising prognostic biomarker in colorectal cancer, and our findings suggest that it could be used in the selection of stage III patients for adjuvant therapy

The impact of ADHD and conduct disorder in childhood on adult delinquency: A 30 years follow-up study using official crime records

<p>Abstract</p> <p>Background</p> <p>Few longitudinal studies have explored lifetime criminality in adults with a childhood history of severe mental disorders. In the present study, we wanted to explore the association between adult delinquency and several different childhood diagnoses in an in-patient population. Of special interest was the impact of disturbance of activity and attention (ADHD) and mixed disorder of conduct and emotions on later delinquency, as these disorders have been variously associated with delinquent development.</p> <p>Methods</p> <p>Former Norwegian child psychiatric in-patients (n = 541) were followed up 19-41 years after hospitalization by record linkage to the National Register of Criminality. On the basis of the hospital records, the patients were re-diagnosed according to ICD-10. The association between diagnoses and other baseline factors and later delinquency were investigated using univariate and multivariate Cox regression analyses.</p> <p>Results</p> <p>At follow-up, 24% of the participants had been convicted of criminal activity.</p> <p>In the multivariate Cox regression analysis, conduct disorder (RR = 2.0, 95%CI = 1.2-3.4) and hyperkinetic conduct disorder (RR = 2.7, 95% CI = 1.6-4.4) significantly increased the risk of future criminal behaviour. Pervasive developmental disorder (RR = 0.4, 95%CI = 0.2-0.9) and mental retardation (RR = 0.4, 95%CI = 0.3-0.8) reduced the risk for a criminal act. Male gender (RR = 3.6, 95%CI = 2.1-6.1) and chronic family difficulties (RR = 1.3, 95% CI = 1.1-1.5) both predicted future criminality.</p> <p>Conclusions</p> <p>Conduct disorder in childhood was highly associated with later delinquency both alone or in combination with hyperactivity, but less associated when combined with an emotional disorder. ADHD in childhood was no more associated with later delinquency than the rest of the disorders in the study population. Our finding strengthens the assumption that there is no direct association between ADHD and criminality.</p

The impact of ADHD symptoms and global impairment in childhood on working disability in mid-adulthood: a 28-year follow-up study using official disability pension records in a high-risk in-patient population

Background Individuals with ADHD have been associated with more employment difficulties in early adulthood than healthy community controls. To examine whether this association is attributable specifically to disturbance of activity and attention (ADHD) or to psychopathology in general, we wanted to extend existing research by comparing the rate of mid-adulthood working disabilities for individuals diagnosed with ADHD as children with the rate for clinical controls diagnosed with either conduct disorder, emotional disorder or mixed disorder of conduct and emotions. Methods Former Norwegian child-psychiatric in-patients (n = 257) were followed up 17–39 years after hospitalization by record linkage to the Norwegian national registry of disability pension (DP) awards. Based on the hospital records, the patients were re-diagnosed according to ICD-10. Associations between the diagnoses, other baseline factors and subsequent DP were investigated using Kaplan–Meier survival analyses and logrank testing. Results At follow-up, 19% of the participants had received a DP award. In the logrank testing, ADHD was the only disorder associated with a subsequent DP, with 30% being disabled at follow-up (p = 0.01). Low psychosocial functioning (assessed by the Children’s Global Assessment Scale) at admission uniquely predicted future DP (p = 0.04). Conclusions ADHD in childhood was highly associated with later receiving a DP. Our finding of worse prognosis in ADHD compared with other internalizing and externalizing disorders in mid-adulthood supports the assumption of ADHD being specifically linked to working disability. Assessment of psychosocial functioning in addition to diagnostic features could enhance prediction of children who are most at risk of future disability