Identifying mismatch repair deficient colon cancer: near perfect concordance between immunohistochemistry and microsatellite instability testing in a large, population-based series
Objective: Establish a mismatch repair (MMR) status of colorectal cancer is essential to enable the detection of Lynch syndrome that underlie and inform prognosis and therapy. current testing usually involves either PCR-based microsatellite (MSI) testing or MMR protein immunohistochemistry (IHC). We aimed to compare the two approaches, a large population-based cohort of stage 2 and 3 cases of colon cancer in Northern Ireland.
Methods and results: Promega pentaplex Using this test, we determined the status of MSI’s four MMR IHC antibody panel. IHC applied to the tumor tissue microarray tumor samples in triplicate and scored manually. Of the 593 cases with available MSI and MMR IHC results, 136 (22.9%) were MSI-H and 135 (22.8%) displayed abnormal MMR IHC.
Concordance was very high, with 97.1% of MSI-H cases showed normal MMR IHC and 97.8% of cases with normal IHC showed MSI-H status. Under-representation of epithelial tumor cells in a sample of the tumor is very inflamed resulting in misclassification of some cases with microsatellite stable normal MMR IHC. MMR IHC revealed a rare case with unusual patterns of expression of MMR proteins, an unusual combination of loss of secondary clonal expression or loss of expression, is further illustrated by immunostaining repeated in all parts of the network.
Conclusions: PCR MSI and MMR IHC testing can be considered equally adept tests to establish the status of MMR / MSI, while aware of the potential pitfalls either method. Methodology selection may depend on the available services and expertise.
Anti-sclerostin monoclonal antibody romosozumab, treatment for osteoporosis, reduce the risk of vertebral fracture and clinical fracture. laser irradiation triggers a variety of effects, including bio-stimulation, which can induce beneficial effects of therapy and biological response. Initially, we performed in vivo experiments to clarify the mechanism better bone healing in bone laser ablated.
Here, we evaluated a comprehensive gene expression and sequence in the Er: YAG laser ablation, bur-drilled, and bones treated controls, and found the laser irradiation is pressed Sost (protein coding: sclerostin) expression in the bone, possibly through stimulation mechanotransducers. Surprisingly, the effect of laser bio-stimulation suppressed the expression of Sost in primary osteogenic cells.
Identifying mismatch repair deficient colon cancer: near perfect concordance between immunohistochemistry and microsatellite instability testing in a large, population-based series
SPARC is a key mediator of TGF-β-induced metastatic kidney cancer
Aberrant expression of transforming growth factor-β1 (TGF-β1) is associated with renal cell carcinoma (RCC) progression by inducing the cancer metastasis. However, downstream effector (s) in the TGF-β signaling pathway is not fully characterized. In this study, the height of secreted protein acidic and rich in cysteine (SPARC) as regulated TGF-β genes in RCC were identified by applying the analysis of genes expressed differently and microarray analysis, we further confirmed these results in a few RCC cell lines.
Clinically, expression of both genes were positively correlated to the RCC patient specimens. Furthermore, increased expression of SPARC is found in all subtypes of RCC and RCC positively correlated with stage and grade. Instead, SPARC expression is inversely proportional to the overall and disease-free survival of patients with RCC, showing SPARC as a powerful prognostic marker of survival of RCC patients. SPARC knock down significantly inhibit invasion and metastasis of RCC cells both in vitro and in vivo.
Similarly, in vitro cell invasion could be reduced by using a specific monoclonal antibody. Mechanically, SPARC activate protein kinase B (AKT) pathway which leads to an increase in the expression of matrix metalloproteinase-2, which can facilitate the invasion of RCC. Overall, our data support the SPARC is an important role of TGF-β signaling networks that underlie the development of RCC and potential therapeutic targets and prognostic markers.