Anti-RXRG monoclonal antibody, clone 2484

The distinction between follicular thyroid carcinomas (FTCs) and follicular-patterned benign lesions is almost impossible on fine-needle aspiration cytology. Furthermore, minimally invasive FTCs (MI-FTCs) with less than 4 vascular invasion foci generally have an excellent prognosis, but there are exceptions and, so far, no molecular marker appears able to identify them reliably. We aimed to distinguish benign lesions from low-and high-risk FTCs by a small-scale combination of genes. The expression analysis of 75 selected genes was performed on 18 follicular adenomas (FAs), 14 MI-FTCs and 6 widely invasive FTC (WI-FTCs). The mutational status of the RAS genes, TERT promoter and PAX8-PPARG rearrangements was also investigated. Seven samples were mutated, namely 3 MI-FTCs and 4 WI-FTCs. Twenty-five genes were differentially expressed (FDR < 0.05) between FAs and WI-FTCs. Six of these (ECM1, RXRG, SDPR, SLC26A4, TIFF3, TIMP1) were also differently expressed among MI-FTCs and FAs or WI-FTCs and were considered to build a classification model, which was tested to classify samples according to their histological class. Hence, 31 out of 38 were correctly classified, and accuracy remained high after cross-validation (27/38). The 2 MI-FTCs incorrectly classified as WI-FTCs harbored both RAS and TERT promoter mutations. The capability of these six genes to stratify benign, low-and high-risk lesions appears to be promising in supporting the diagnosis of indeterminate thyroid nodules.

Objective. To use microarray analyses of gene expression to characterize the synovial molecular pathways regulated by the arthritis regulatory locus Cia25 and to determine how it operates to control disease severity and joint damage. Methods. Synovial tissues from DA rats and DA. ACI(Cia25) rats obtained 21 days after induction of pristane-induced arthritis were used for RNA extraction and hybridization to Illumina RatRef-12 Expression BeadChips (22,228 genes). Genes with a P value <= 0.01 and a fold difference in expression >= 1.5 between DA rats and DA. ACI(Cia25) rats were considered significant. Results. Interleukin-1 beta (IL-1 beta) (7.4-fold), IL-6 (67-fold), Ccl2, Cxcl10, Mmp3, Mmp14, and innate immunity genes were expressed at increased levels in DA rats and at significantly lower levels in DA. ACI( Cia25) congenic rats. DA. ACI(Cia25) rats had increased expression of 10 nuclear receptor (NR) genes, including those known to interfere with NF-kappa B activity and cytokine expression, such as Lxra, Pparg, and Rxrg. DA. ACI(Cia25) rats also had increased expression of NR targets, suggesting increased NR activity. While Vdr was not differentially expressed, a Vdr expression signature was detected in congenic rats, along with up-regulation of mediators of vitamin D synthesis. Conclusion. This is the first description of the association between increased synovial levels of NRs and arthritis protection. The expression of NRs was inversely correlated with the expression of key mediators of arthritis, suggesting reciprocally opposing effects either via NF-kappa B or at the genomic level in the synovial tissue. We consider that the NR signature may have an important role in maintaining synovial homeostasis and an inflammation-free tissue. These processes are regulated by the Cia25 gene and suggest a new function for this gene.