Nrf2 and Her3 co-expression in cholangiocarcinoma:Possible biological pathways for potential therapeutic approach

To the Editor:Cholangiocarcinomas(CCAs)are heterogeneous group of malignancies,encompassing intrahepatic CCA(iCCA),and extrahepatic CCA(eCCA);they are also classified into common hepatic duct cholangiocarcinoma(CHDCCA),choledocus extrapancreatic cholangiocarcinoma(EPCCA)and choledocus intrapancreatic cholangiocarcinoma(IPCCA)and,finally,gallbladder carcinoma(GBCCA).CCAs are relatively uncommon but.

Autoimmune gastritis:Pathologist's viewpoint

Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic(and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and(intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integratingendoscopy, serology, histology and molecular profiling.

HER2 heterogeneity in gastric/gastroesophageal cancers: From benchside to practice

HER2 is overexpressed in approximately 10%-20% of gastric and gastroesophageal junction carcinomas. In these types of cancer, accurate assessment of HER2 status is mandatory, for selecting patients who may benefit from targeted therapies with anti-HER2 drugs such as Trastuzumab. This manuscript focuses on HER2 in gastric carcinogenesis, on optimal evaluation of HER2 and on the possible causes which may contribute to inaccurate HER2 evaluation. Similarly to breast cancer HER2 evaluation, standardization of HER2 testing in gastric cancer is necessary in diagnostic practice. The three principle aspects which require consideration are:(1) the choice of sample with regards to cancer morphology- intestinal vs diffuse areas;(2) the choice of scoring criteria- use of HER2 scoring criteria specific for gastric cancer; and(3) the choice of HER2 evaluation methods- use of an algorithm in which both immunohistochemistry and in situ hybridization play a role. Problematic issues include:(1) pre-analytic variables with particular emphasis on fixation;(2) recommended methodology for HER2 assessment(immunohistochemistry vs in situ hybridization);(3) HER2 heterogeneity both within the primary tumor and between primary tumor and metastases;(4) reliability of biopsies in HER 2 evaluation; and(5) quantity of sample(FFPE blocks from surgical specimens or endoscopic biopsies) necessary for an adequate assessment.

Assessing the quality of studies in meta-analyses: Advantages and limitations of the Newcastle Ottawa Scale

One of the most important points in the meta-analyses is certainly represented by the assessment of the quality of the studies included in such research. The meta-analyses are considered the highest level of evidence in science. Also for this reason, the quality of the studies included should be accurately evaluated by standardized tools. The overall results of the metaanalysis depend indeed also on a rigorous evaluation of the studies quality. Among all the possible tools for this complex evaluation, the Newcastle Ottawa Scale(NOS) is one of the most used worldwide, above all for observational studies. In this review, we will discuss the strengths and limitation of the NOS, also on the basis of the branch of science in which it has been applied.

Noncoding RNAs as drivers of the phenotypic plasticity of oesophageal mucosa

The histological commitment of the lower oesophageal mucosa largely depends on a complex molecular landscape. After extended inflammatory insult due to gastroesophageal reflux disease,squamous oesophageal mucosa may differentiate into columnar metaplastic mucosa. In this setting,the presence of intestinal metaplasia is considered the starting point of Barrett's carcinogenetic cascade. Aside from secondary prevention strategies for Barrett's mucosa(BM) patients,there are multiple endoscopic ablative therapies available for BM eradication and for the replacement of metaplastic epithelia with a neosquamous mucosa. However,BM frequently recurs in a few years,which supports the notable phenotypic plasticity of the oesophageal mucosa. In recent years,several reports pinpointed a class of small noncoding RNAs,the micro RNAs(mi RNAs),as principal effectors and regulators of oesophageal mucosa metaplastic(and neoplastic) transformation. Because of mi RNAs notable stability in fixed archival diagnostic specimens,expression profiling of mi RNAs represent an innovative diagnostic,prognostic and predictive tool in the stratification of phenotypic alterations in the oesophageal mucosa.

HER2的免疫组织化学诊断和ASCO／CAP指南中的几个问题

HER2基因在15％～20％的乳腺癌扩增到正常的2—20倍，导致HER2蛋白在肿瘤细胞膜上的表达大量增加。这使HER2成为理想的靶向治疗靶点。曲妥珠单抗（商品名为赫塞汀）是一个针对HER2的单克隆抗体，它对HER2阳性的乳腺癌具有明显的抗癌效应，特别是当它与其他细胞毒性抗癌药物联用时，能减少早期HER2阳性乳腺癌的复发率至50％。