Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways / 中华医学杂志(英文版)

BACKGROUND@#Thymic carcinomas (TCs) and thymic neuroendocrine neoplasms (TNENs) are two aggressive subtypes of thymic malignancy. Traditional therapy for advanced TCs and TNENs has limited outcome. New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches.@*METHODS@#We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017. Patient samples were sequenced using a 324-gene platform with licensed technologies. In this study, we focused on clinically relevant genomic alterations (CRGAs), which are previously proven to be pathogenic alterations, to identify the pathology-specific mutational patterns, prognostic signatures of TCs and TNENs.@*RESULTS@#The mutational profiles between TCs and TNENs were diverse. The genetic alterations that ranked highest in TCs were in CDKN2A, TP53, ASXL1, CDKN2B, PIK3C2G, PTCH1, and ROS1 , while those in TNENs were in MEN1, MLL2, APC, RB1 , and TSC2 . Prognostic analysis showed that mutations of ROS1, CDKN2A, CDKN2B, BRAF, and BAP1 were significantly associated with worse outcomes in TC patients, and that mutation of ERBB2 indicated shortened disease-free survival (DFS) and overall survival (OS) in TNEN patients. Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control, chromatin remodeling/DNA methylation, phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), and receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase (MAPK) signaling.@*CONCLUSION@#We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors, and identified the pathology-specific mutational patterns, prognostic signatures, and potential therapeutic targets for TCs and TNENs.

Consistency of ALK Ventana-D5F3 immunohistochemistry interpretation in lung adenocarcinoma among Chinese histopathologists / 中华病理学杂志

Objective@#To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy.@*Methods@#This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS.@*Results@#There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109).@*Conclusion@#There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.

Role of Irbesartan on cardiac endothelial-to-mesenchymal transition in diabetic rats / 中华肾脏病杂志

Objective To explore the effect of irbesartan on cardiac endothelial-mesenchymal transition (EndMT) in diabetic rats.Methods The model of diabetic rat was induced by intraperitoneal injection with streptozotocin (STZ,35 mg/kg) in spontaneous hypertensive rats (SHR).Diabetic rats were divided into diabetic group and the Irbesartan treated group.The pathological changes were investigated by fluorescence microscope and electron microscope.The EndMT was studied in human aortic endothelial cells (HAEC) exposure to high glucose.The concentration of angiotensin Ⅱ in the supernatant was detected by radioimmunoassay.Immunofluorescence staining was performed to detect the co-localization of CD31 and FSP1.Results The significant myocardial fibrosis was presented in the diabetic group.Endothelial protrusions were prominent feature in myocardial microvascular of diabetic rat compared with the control group rats.Double staining of HAEC showed co-localization of CD31 and FSP1,which was decreased by the treatment of Irbesartan (P ＜ 0.05).When HAEC was exposed to high glucose,it showed some cells acquired spindle-shaped morphology and lost CD31 staining,and FSP1 and α-SMA protein expression levels were markedly upregulated,which attenuated by the treatment of Irbesartan.Conclusion Irbesartan might prevent diabetes from myocardial fibrosis via inhibition of EndMT in diabetic rats.

Multi-slice spiral CT findings of Castleman disease / 中华放射学杂志

Objective To analyze the CT imaging features of Castleman disease and enhance our knowledge of Castleman disease.Methods Twenty two patients with lymph node biopsy-proved or surgeryproved Castleman disease were retrospectively reviewed in this study.Of the 22 patients,18 had localized lesion and 4 patients had multicentric lesions.Correlation was made between CT and pathologic findings.Results Eighteen patients with localized Castleman disease had the hyaline-vascular type and showed well-circumscribed masses with soft-tissue density [mean CT value,(45 ± 16) HU],punctate or bifurcate calcification and linear low-density areas on non-enhanced CT images.All localized masses showed significant enhancementwith an increase of(56 ± 22)HU on arterial phase and showed residual enhancement and some low-density areas on delayed phase.Enhancing patterns were variable,including homogeneous enhancement,gradual enhancement from the edge to the center of mass and heterogeneous enhancement.Four patients with localized lesion demonstrated enhancing vessels around masses.Four patients with muhicentric CD belonged to the plasma cell type and had multiple enlarged lymph nodes.Plasma cell type masses with homogeneous density also showed enhancement after injection of contrast media but appeared to reveal a less increase of (32 ± 10) HU than the hyaline vascular type.Conclusions The localized Castleman disease showed certain characteristics on CT imaging includingcalcification and contrast enhancing patterns,which could help in the differential diagnosis of this disease.The muhicentric Castleman disease did not reveal any useful imaging features.

EXPRESSION AND LOCALIZATION OF THROMBOMODULIN IN HUMAN FETAL LUNG / 解剖学报

Objective\ To detect thrombomodulin protein in 18 weeks human fetal lung. Methods\ SP method was used in the study. Results\ It showed that, in fetal lung tissues, thrombomodulin expressed in the endothelial cells of capillaries surrounding the primary alveoli, but it was absent in cuboid cells and ciliated\|columnary epithelium cells and cartilage. Conclusion\ Our results suggest that thrombomodulin does not exist in middle and late stage's human fetal lung.\;