HER2 in gastric cancer: Comparative analysis of three different antibodies using whole-tissue sections and tissue microarrays

AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We present a comparative analysis of three anti-HER2 antibodies(HercepTest,4B5 and SP3)using TMA and whole-tissue sections prepared from the same paraffin blocks of 199 gastric adenocarcinomas operated upon between January 2004 and December2008 at a Brazilian cancer hospital.The data on the patients’age,sex,the anatomical location of the tumor and the Lauren’s histological classification were collected from clinical and pathological records.The immunohistochemical(IHC)results were examined by two pathologists and the cases were classified as positive(3+),equivocal(2+)and negative(0 or 1+),according to the criteria of the IHC scoring system of gastric cancer.TMAs and whole-tissue sections were evaluated separately and independently.All cases yielding discordant IHC results and/or scored as 2+were subjected to dual-color in situ hybridization in order to determine the final HER2 status.Besides determining the sensitivity and predictive value for HER2-positive status,we measured the accuracy of each antibody by calculating the area under the receiver operating characteristic(ROC)curve.The agreement between the results obtained using the TMAs and those obtained using the whole-tissue sections was assessed by means of Kappa coefficient.RESULTS:Intratumoral heterogeneity of HER2 expression was observed with all antibodies.HER2-positive expression(3+)in the whole-tissue sections was observed in 23 cases(11.6%)using the 4B5 antibody,in 18 cases(9.1%)using the SP3 antibody and in 10 cases(5.1%)using the HercepTest antibody.In the TMAs,11 positive cases(5.6%)were identified using SP3 antibody,9(4.6%)using the 4B5 antibody and 6(3%)using the HercepTest antibody.The sensitivity using whole-tissue sections and TMA,respectively,was 95.2%and 42.9%with 4B5,90.5%and 66.7%with SP3 and 47.6%and42.9%with HercepTest.The accuracy,calculated from the area under the ROC curve,using whole-tissue sections and TMA,respectively,was 0.91 and 0.79 by 4B5,0.86 and 0.80 by SP3 and 0.73 and 0.71 by HercepTest.The concordance of the results obtained using wholetissue sections and TMA was 97.4%(Kappa 0.75)using HercepTest,85.6%(Kappa 0.56)using SP3 and 84.1%(Kappa 0.38)using 4B5.CONCLUSION:The use of the 4B5 antibody on wholetissue sections was the most accurate IHC method for evaluating HER2 expression in gastric adenocarcinoma.

2q37.3 Deletion with Complex Heart Defects Suggesting Interruption of Early Ventricular Looping

A maternally inherited 828 kb microdeletion of 2q37.3 manifested in a 3-week-old premature boy as left juxtaposition of the atrial appendages associated with tricuspid atresia,double outlet infundibulum,subvalvar pulmonary atresia,large secundum atrial septal defect,and right aortic arch with mirror-image branching,consistent with developmental arrest early in heart looping.To the best of our knowledge,no previous 2q37 deletion syndrome has been reported with such a severe cardiac dysmorphology.Hence,this case adds to the cardiac phenotypes identified in 2q37 deletion syndrome.

Barrett食管患者人群中结肠直肠癌的发病率

Objective. Previous studies have shown a positive association between colorectal cancer and Barrett’s oesophagus, but this association is disputed. No population-based studies have examined the incidence of this cancer in patients with Barrett’s oesophagus. Material and methods. The present study comprised a population-based cohort of patients with Barrett’s oesophagus (constructed using pathology reports of all oesophageal biopsies in Northern Ireland 1993-99; cohort subclassified according to whether specialized intestinal metaplasia (SIM) was present, absent, or not commented on in biopsies). Cases of colorectal cancer were identified by linking with the Northern Ireland Cancer Registry. The comparison group used was the general population in Northern Ireland. Results. A total of 2969 patients with Barrett’s oesophagus were followed for a total of 14,014 person-years (mean 4.7 years). SIM was present in 1670 patients (56.2%), absent in 545 (18.4%) and not commented on in 754 (25.4%). Colorectal cancer was diagnosed in 39 patients; 22 patients had cancer diagnosed at least 6 months after diagnosis of Barrett’s oesophagus. There was no increased risk of colorectal cancer: the standardized incidence ratio (SIR) for cancer diagnosed at least 6 months after entry into the cohort was 0.82 (95%CI, 0.48-1.17); this risk did not alter with SIM status or gender. To assess a possible effect of diagnostic bias, we calculated SIRs for cancers occurring after at least 3 months, after at least 1 month and at any time after diagnosis of Barrett‘s oesophagus. These were 0.94 (0.57-1.30), 1.09 (0.69-1.48) and 1.46 (1.00-1.92), respectively. Conclusions. The incidence of colorectal cancer was not elevated in patients with Barrett’s oesophagus. Diagnostic bias may explain why previous studies have found an association.

Survival trends of patients with non-metastatic gastric adenocarcinoma in the US and European countries:the impact of decreasing resection rates

Background:We previously observed decreasing resection rates of nonmetastatic gastric adenocarcinoma(GaC)in the US and some European countries.If and to what extent these trends affect the trends in overall survival(OS)of patients with non-metastatic GaC at the population level remain unclear.This large international population-based cohort study aimed to assess the impact of the previously observed decreasing resection rates on multivariable-adjusted trends in the long-term OS of patients with non-metastatic GaC.Methods:Individual-level data of patients with non-metastatic GaC were obtained from the national cancer registries of the Netherlands,Belgium,Sweden,Norway,and Slovenia,and the US Surveillance,Epidemiology,and End Results database.We analyzed data for each country separately.Associations between year of diagnosis and OS were assessed using Cox proportional hazards regression model with adjustment for multiple prognostic variables,with and without including resection and chemotherapy as potential explanatory variables.Results:A total of 66,398 non-metastatic GaC patients diagnosed in 2003-2016 were analyzed,with an accumulated follow-up of 172,357 person-years.Without adjustment for resection,OS was improved only slightly in the US[hazard ratio(HR)_(per year)=0.99;HR_(≥vs.<2010)=0.96],and no improvement was observed in the investigated European countries,with OS even worsening in Sweden(HR_(per year)=1.03;HR_(≥vs.<2010)=1.17).After adjusting for resection,the increasing OS trend became stronger in the US(HR_(per year)=0.98;HR_(≥vs.<2010)=0.88),and the temporal trend became insignificant in Sweden.In Slovenia(HR_(per year)=0.99;HR_(≥vs.<2010)=0.92)and Norway(HR_(per year)=0.97;HR_(≥vs.<2010)=0.86),improved OS over time emerged after resection adjustment.Improved OS in patients undergoing resection was observed in the US,the Netherlands,and Norway.Adjustment for chemotherapy did not alter the observed associations.Stratified analyses by tumor location showedmostly similar resultswith the findings in all patients with non-metastatic GaCs regarding the associations between year of diagnosis and survival.Conclusions:OS of patients with non-metastatic GaC mostly did not improve in selected European countries and was even worsened in Sweden,while it was slightly increased in the US in the early 21st century.Progress in OS of patients with non-metastatic GaC seems to have been impeded to a large extent by decreasing rates of resection.