Background:The aim of this study was to compare gene copy number (GCN) and protein expression of MET and to evaluate their prognostic roles in gastric carcinomas.Methods:MET protein expression and gene amplification (GA) status were determined by immunohistochemistry (IHC) and silver in-situ hybridisation (SISH), respectively, in a large series of gastric carcinoma.Results:Protein overexpression was observed in 104 of 438 cases, with IHC 2+ in 94 and IHC 3+ in 10, and high polysomy of chromosome 7 and GA were found in 61 and 13 of 381, respectively. Direct comparison revealed a significant correlation between high level of protein expression and increased GCN. All cases with GA showed protein overexpression. Furthermore, all with IHC 3+ showed GA except 1, even which could be categorised as GA according to the ASCO/CAP guideline for human epidermal growth factor receptor 2 assessment. IHC 3+ and GA were significantly associated with poor prognosis.Conclusion:MET IHC reflects well on GA, and therefore, it could be a primary screening test for patient selection for anti-MET therapy if GA is a major determinant of drug responsiveness. Also, the prognostic role of MET indicates that anti-MET therapy is a very promising modality in adjuvant treatment for gastric cancer.
Background:In preclinical gastric cancer (GC) models, FGFR2 amplification was associated with increased tumour cell proliferation and survival, and drugs targeting this pathway are now in clinical trials.Methods:FGFR2 FISH was performed on 961 GCs from the United Kingdom, China and Korea, and the relationship with clinicopathological data and overlap with HER2 amplification were analysed.Results:The prevalence of FGFR2 amplification was similar between the three cohorts (UK 7.4%, China 4.6% and Korea 4.2%), and intratumoral heterogeneity was observed in 24% of FGFR2 amplified cases. FGFR2 amplification was associated with lymph node metastases (P<0.0001). FGFR2 amplification and polysomy were associated with poor overall survival (OS) in the Korean (OS: 1.83 vs 6.17 years, P=0.0073) and UK (OS: 0.45 vs 1.9 years, P<0.0001) cohorts, and FGFR2 amplification was an independent marker of poor survival in the UK cohort (P=0.0002). Co-amplification of FGFR2 and HER2 was rare, and when high-level amplifications did co-occur these were detected in distinct areas of the tumour.Conclusion:A similar incidence of FGFR2 amplification was found in Asian and UK GCs and was associated with lymphatic invasion and poor prognosis. This study also shows that HER2 and FGFR2 amplifications are mostly exclusive.
Ultrasound as a widely available radiation-free imaging method would be preferable for assessing inflammatory activity of CD, particularly since the ultrasound findings correlate significantly with a histopathological scoring system.
Increasing evidence has demonstrated that increased expression of cyclin-dependent kinase regulatory subunit 1B (CKS1B) is associated with the pathogenesis of many human cancers, including colorectal cancer (CRC). However, the regulatory mechanisms underlying the expression of CKS1B in CRC are not completely understood. Here, we investigate the role played by microRNAs in the expression of CKS1B and carcinogenesis in CRC. Among the six microRNAs predicted to target CKS1B gene expression, only miR-1258 was revealed to downregulate CKS1B expression through binding to its 3’-UTR region, as ectopic miR-1258 expression suppressed CKS1B expression and vice versa. In CRC, miR-1258 expression also decreased cell proliferation and migration in vitro and tumor growth in vivo, similar to cells with silenced CKS1B expression. Considering the highly increased levels of CKS1B and decreased expression of miR-1258 in tumors from CRC patients, these findings suggest that miR-1258 may play tumor-suppressive roles by targeting CKS1B expression in CRC. However, the therapeutic significance of these findings should be evaluated in clinical settings.
Purpose: To evaluate the diagnostic results of different ultrasound techniques: B-scan, color-coded Doppler sonography (CCDS) and contrast-enhanced ultrasound in the diagnosis of abdominal aortic dissection in comparison to multislice computed tomography (MS-CT). Materials and methods: Between March 2006 and December 2008, 35 patients (28 males, 7 females) with a mean age of 58 years (range 37-87 years) with abdominal aortic dissection and 15 patients (11 males, 4 females) with a mean age of 53 years (range 42-78 years) without abdominal aortic dissection as a control group were examined with B-scan, CCDS and contrastenhanced ultrasound (CEUS) after injection of 1.0-1.2 cc of SonoVue (Bracco, Italy). The examinations were performed using a Sequoia 512 (Siemens/Acuson, Mountain View) system with CPS software. Standardized MS-CTA using a 16 or 64 row scanner (Somatom Sensation 16 or 64, Siemens Medical Systems, Forchheim, Germany) served as the reference standard.Results: The sensitivity of B-scan and CCDS for detecting abdominal aortic dissections were both 23/35 (68%); for contrastenhanced ultrasound it was 34/35 (97%). Dissection membrane, differentiation of true and false lumen and flow direction within the true and false lumen were better detected by CEUS than by CCDS. The lack of angle dependence of the US probe and lack of flow and pulsations artifacts in CEUS made the examination procedure easier. All findings were confirmed by MS-CT.Conclusion: With contrast-enhanced ultrasound, diagnostic accuracy sensitivity and specificity for the diagnosis of abdominal aortic dissections is improved as compared to B-scan and CCDS. Dissection membrane and flow within the true and false lumen are clearly differentiated by CEUS. Thus CEUS is a promising alternative for patients whose condition does not allow an examination by CTA.
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