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Background and purpose: Microsatellite instability (MSI) and mismatch repair (MMR) defects have attracted much attention recently as one of the important biomarkers for pan-tumor immunotherapy such as colorectal cancer (CRC). Conventiona methods for MSI detection with polymerase chain reaction (PCR) often require non-tumor controls as well as a long turnaround time. The IdyllaTM system as a fully automated quantitative PCR unit with a turnaround time of only 2.5 h should be proved for its reliability among Chinese CRC patients before application. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples were collected from 87 CRC patients in Fudan University Shanghai Cancer Center from March 2017 to March 2019 and were subjected to detect MMR protein expression and MSI using immunochemistry (IHC), conventional PCR (Promega MSI analysis) and the IdyllaTM MSI system, respectively. Results: Of the 87 CRC patients enrolled, 56 cases were identified to be deficient MMR (dMMR)/MSIhigh (MSI-H) and 31 to be proficient MMR (pMMR)/microsatellite stable (MSS) by both IHC and Promega MSI analysis. However, 4 cases with dMMR/MSI-H were determined to be MSS and one case with pMMR/MSS to be MSI-H using IdyllaTM MSI system, yielding a sensitivity of 92.9% (52/56), specificity of 96.8% (30/31) and an overall concordance of 94.3% (82/87). Then, the above five discordant cases were re-examined using IdyllaTM with resection tissues, as a result, four cases with ≥20% tumor contents changed to be consistent with IHC/Promega MSI assay, however, there was still one inconsistent case with only 5% tumor content. Subsequently, the case was reconfirmed using IdyllaTM with enriched tumor tissue by macro dissection, as expected, the result was demonstrated to be MSI-H, consistent with Promega MSI analysis and IHC. Furthermore, repeatability of the IdyllaTM MSI assay was proved to be reliable in 5 cases with various tumor contents (20%-60%). Conclusion: The IdyllaTM MSI system provides a fast, reliable and fully automated solution to MSI detection in Chinese CRC patients with high sensitivity, specificity and reproducibility, especially for CRC with more than 20% tumor contents. [ABSTRACT FROM AUTHOR]

Objective To compare the histological characteristics of porcine pancreatic elastase （PPE） induced abdominal aortic aneurysms（AAA) and angiotensin Ⅱ（AngⅡ) induced AAA in mice. Methods In the PPE group, the mouse abdominal aorta segment from the infrarenal abdominal aorta to the iliac artery was isolated and its branch arteries were ligated to avoid leakage during PPE perfusion. We perfused the isolated aorta segment with a PPE solution at a concentration of 1. 5 U/mL for 5 min and then closed the abdominal cavity. The diameter of the abdominal aorta was measured before and 14 days after the surgery, and the perfusion segment of the arteries was collected at day 14 after the surgery. The histological characteristics of the aneurysm were analyzed and graded by histological and immunohistochemical methods. In the AngⅡ group， ten apolipoprotein E knockout mice were prepared， and AngⅡ [1 000 ng/(kg·min)] was infused with osmotic pumps for 28 days. The aorta was separated and the aneurysm aorta segment was analyzed. The wild type mice were used as normal health controls. Results In the PPE group， the diameter of the PPE perfused aorta segments increased and was significantly larger than the basal diameter［（0. 52±0. 02）mm vs. （1. 23±0. 11）mm］at day 14 after surgery. All the ten mice developed AAA after PPE application. The histological results showed typical pathological features of AAA in PPE perfused mice， such as elastic fiber breakage， smooth muscle exhaustion， and increased inflammation. Six of the ten mice developed aneurysms after AngⅡ infusion（6/10). The aneurysms/dilatations were mostly in the suprarenal abdominal aorta, but also in the thoracic aorta and aortic arch. The histology analysis showed that the formation of arterial dissection was common after Ang Ⅱ infusion， and the typical vascular“false lumen”was found. The breakage of elastic fibers, the exhaustion of smooth muscle damage, and the inflammatory response were not as typical as the PPE model in AngⅡ perfused animals. Conclusion The histological characteristics of PPE induced AAA are very typical and well present the inflammatory process in the development of aneurysm. The AngⅡ model is suitable for the study of aneurysms combined with aortic dissection. Both models have their own advantages and can complement each other. [ABSTRACT FROM AUTHOR]