Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms

Abstract

Objective Intracranial arterial dolichoectasia (IADE), also called dilatative arteriopathy of the brain, is defined as an increase in length and diameter of intracranial arteries. Abdominal aortic aneurysm and ectasia of coronary arteries have been reported in association with IADE. In both conditions, a dysfunction of matrix metalloproteinases (MMP)‐2, ‐3, and ‐9 have been found. Our aim was to investigate these MMP pathways in stroke patients with IADE. Methods Five hundred ten Caucasians patients with brain infarction were consecutively recruited at 12 centers. The diagnosis of IADE was made by consensus between 2 neurologists based on magnetic resonance imaging scans. Determination of MMP‐2, ‐3, and ‐9 plasma levels was centralized in 1 laboratory. Because we found a threshold effect of MMP‐3 plasma levels with the risk of IADE, determination of the MMP‐3 5A/6A polymorphism was carried out. Results IADE was identified in 12% of stroke patients. There was no association of IADE with mean MMP‐2, ‐3, and ‐9 plasma levels. After categorization of MMP plasma levels into tertiles, we found a higher risk of IADE with the lowest MMP‐3 tertile (adjusted odds ratio [OR], 2.48; 95% confidence interval [CI], 1.17–5.23). In genotype analysis, there was a significant additive effect of the 5A allele on the risk of IADE, with an adjusted OR of 1.62 (95% CI, 1.03–2.55). Interpretation In this cohort of stroke patients of Caucasian ancestry, IADE was associated with low MMP‐3 plasma levels and with the 5A/6A polymorphism of the promoter region of MMP‐3. These results suggest that MMP‐3 may play a role in IADE. ANN NEUROL 2010;67:508–515

A Panel of Four miRNAs Accurately Differentiates Malignant from Benign Indeterminate Thyroid Lesions on Fine Needle Aspiration

“…Therefore, mutation analysis alone is insufficient to classify most malignant indeterminate lesions on FNA. Several reports have identified gene panels ranging from 6 to 105 genes with high sensitivity and specificity at differentiating benign from malignant thyroid tissue samples (31)(32)(33)(34)(35)(36). Although these findings are encouraging, the predictive accuracy of these gene panels in FNA samples in a real-world setting remains limited, as these were validated on small cohorts of patients and did not analyze samples with indeterminate cytology on FNA.…”

TMPRSS4 correlates with colorectal cancer pathological stage and regulates cell proliferation and self-renewal ability

“…In breast cancer, higher expression of TMPRSS4 was associated with positive lymph node metastasis, larger tumor size, advanced pathological grade, and shorter overall and disease-free survival; 16 in non-small cell lung cancer, overexpression of TMPRSS4 in patients with squamous histology was associated with poor prognosis; 24 in malignant thyroid neoplasm, TMPRSS4 was identified to be a diagnostic marker. 25 Of note, Jung et al had reported TMPRSS4 was upregulated in colon cancer.…”

Hepatocyte Growth Factor Activator Inhibitor Type 1 Regulates Epithelial to Mesenchymal Transition through Membrane-Bound Serine Proteinases

“…TMPRSS4, which was initially termed TMPRSS3, was identified as a protein up-regulated in pancreatic cancer (24). It is also up-regulated in gastric, colon, and thyroid cancers (24,36), suggesting that TMPRSS4 may have a role in tumor progression. In fact, recent study has revealed that overexpression of TMPRSS4 in colon cancer cells enhances invasiveness and induces EMT (20), findings that are in accord with our present observations.…”