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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.
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Objective The aim of this study was to illuminate effects of LncRNA MEG3 on the viability and apoptosis of hu-man glioma cells as well as the mechanisms involved. Methods The expressions of MEG3 and microRNA-21(miR-21) in normal human astrocytes cell line(NHAs)and human glioma cell line(U87)was detected by Real-Time quantitative polymerase chain reac-tion(RT-qPCR). U87 cells was transfected with MEG3 plasmid alone or transfected with both MEG3 plasmid and miR-21 mimic, cell viability was detected by CCK-8 assay,cell apoptosis was detected by TUNNEL,and the expression of Bcl-2/Bax and Cleaved caspase-3 in cells was detected by Western blot. Results Compared with NHAs,the expression of MEG3 in U87 was significantly decreased and the expression of miR-21 was significantly increased. Overexpression of MEG3 significantly decreased the expression of miR-21 in U87 cells,inhibited the viability of U87 cells,decreased the level of Bcl-2/Bax,increased the content of Cleaved-caspase-3 to promote apoptosis;Co-overexpression of MEG3 and miR-21 significantly increased the viability of U87 cells,elevated Bcl-2/Bax levels,and decreased the expression of Cleaved caspase-3 to inhibit apoptosis. Conclusion Overexpression of MEG3 reduces the viability and promotes apoptosis of glioma cells by inhibiting miR-21.
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FoxM1 is a specific transcription factor related to proliferation .Previous studies have found that FoxM1 can enhance the proliferation ,metastasis and invasion of cancer cells ,and play a crucial role in canc-er.Recent studies indicate that the abnormal expression of FoxM 1 plays an important role in breast cancer ,and its overexpression is negatively correlated with the overall survival of patients .For the early diagnosis of breast canc-er,clinical prognosis and study on combination therapy provides a new direction .This article reviews the relation-ship between FoxM1 and breast cancer .
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Objective To investigate the expression of astrocyte elevated gene -1( AEG-1) and matrix metallopeptidase 9(MMP-9)in colorectal tissues and evaluate its correlation with clinical pathologic factors of colorectal cancer.Methods AEG-1 and MMP-9 expression in normal colorectal mucous (n=45),low-grade adenoma(n=31),high-grade adenoma(n=15)and colorectal carcinoma(n=146)were examined by immuno-histochemistry .Statistical analyses were applied to test the significance of its expression .Results AEG-1 ex-pression levels were gradually elevated in normal tissues ,low-grade adenoma ,high-grade adenoma and colorec-tal carcinoma respectively .Furthermore ,there was a similar trend for MMP -9from normal mucous to adenoma and carcinoma .Statistical analysis revealed that AEG -1 expression was markedly correlated with the UICC stage,T classification,N classification,M classification,and histological differentiation in the colorectal cancer pa-tients,but not with age,gender,tumor location and tumor size.In addition,AEG-1 expression was positively cor-related with the MMP-9 expression in colorectal cancer .Besides,those patients with high AEG-1 and MMP-9 levels had shorter survival time ( P<0 .05 ) .Conclusion AEG-1 may be involved in carcinogenesis and pro-gression of colorectal carcinoma and can be a novel prognostic biomarker in patients with colorectal carcinoma .
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Objective To investigate the role of HMGA2 expression and epithelial to mesenchymal cell transformation in the regulation of TGF -β1 in human gastric cancer cells .Methods Human gastric cancer cell SGC-7901 was treated by TGF-β1 at different time points(0,3,6,24,48,72 h).We observed the changes in cell morphology of SGC-7901 through the microscope;HMGA2 assay,E-cadherin,Vimentin protein expression wereperformedbyWesternblot;cellinvasioncapabilitywasanalyzedbytranswellchamberassay.Results (1) With the prolonged duration of action of TGF -β1,SGC-7901 changes in cell morphology ,cells gradually be-came longer and larger.(2)In the role of TGF-β1,gastric cancer cells SGC -7901 are varying degrees of HM-GA2 expression and E -cadherin、Vimentin.HMGA2 protein begun to express from 0h to 6hrs.and HMGA2 pro-tein became the strongest at 6hrs and decreased slightly from 24hrs.E-cad protein expression at 0h begun at 3hrs highest expression ,and the reduction started from 3hrs.Vimentin protein was the highest at 48hrs then gradu-ally decreased.Conclusion In the TGF-β1 induced the process of epithelial to mesenchymal cell transforma-tion in gastric cancer cells SGC -7901 ,HMGA2 protein play an important role .HMGA2 can be used as snail pro-moter,combined with Smads ,promotes the process of epithelial -mesenchymal transformation .HMGA2 may also be regulated by Wnt /β-Catenin signaling pathway on growth and apoptosis of tumor cells .
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Objective To investigate the expression level of human epididymis protein 4 ( HE4 ) in se-rous ovarian cancer tissues and its relationship with clinicopathological features .Methods The expression level of HE4 in 140 serous ovarian cancer patients and its relationship with clinicopathological features were detected by immunohistochemistry.To compare the correlation between HE4 and CA125, the histological expressionOf CA125 was also detected by IHC .Results the positive expression rate of HE 4 and CA125 in moderately and poorly differentiated serous ovarian cancer tissues were respectively 89.76%and 81.89%;the positive expression rate in well differentiated group were respectively 46.61% and 15.38%,in the advanced stages were 92.44%and 83.19%,in the early stages were 47.62%and 33.33%.the positive expression rate of lymphatic metastasis were 95.65%and 84.35%,without lymphatic metastasis were 40.00%and 36.00%,the positive expression rate of peritoneal implantation were 90.00% and 87.27%, without peritoneal implantation were 70.00% and 33.33%;the positive expression rate of ascites were 89.76% and 79.53%,without ascites were 46.15% and 38.46%.Besides,the positive expression rates of HE4 and CA125 were 86%and 76%,the differences were sta-tistically significant.Both the positive expression in ovarian cancer are correlated positively (P0.05).Conclusion The expression of HE4 in serous ovarian cancer is related with FI-GO stages,the degree of tumor differentiation ,lymph node metastasis and ascites .
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It has been demonstrated that astrocyte elevated gene 1 ( AEG-1 ) can promote tumor initia-tion and progression .Over expression of AEG -1 is correlated with tumor angiogenesis ,metastasis and chemother-apy resistance of tumor cells of different origins .The present article is a review on the mechanism of AEG -1 me-diated drug resistance .Studies have shown that AEG -1 participates in carcinogenesis through Ha -ras,myc,NF-κB and PI3K/Akt signalling pathways .AEG-1 can also promote autophagy through activating AMP Kinase . Other researchers demonstrate that AEG -1 promotes MDR1 protein translation by up-regulating MDR1 mRNA expression ,and thus increases polyribosome .It is testified that AEG-1 can influence drug susceptibility and ex-pression of MDR gene as a RNA binding protein .Multiple functions of AEG -1 in drug resistance in multiple cancers demonstrate that AEG -1 can be used as a novel target for antitumor drugs .
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Tumor metastasis and invasion of cancer are the leading causes of death in patients .The processes of tumor metastasis and invasion involves a variety of factors in which epithelial -to-myofibroblast transition( EMT) plays an important role .Transcription factor Snail as EMT of tumor cell key regulator has played an important role .Through the study of Snail regulating EMT of tumor cell signaling pathways will help us under -stand the mechanisms of tumor invasion and metastasis better and provide a basis for finding effective targets .
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Objective:To study the correlation of thymidine phosphory la se(TP) expression with histological parameters and microvessel density(MVD) in t umor stroma of oral squamous cell carcinoma(OSCC).Methods:52 cas es of oral squamous cell carcinoma and 10 cases of normal oral mucosa were immun ohistochemically stained with a SP method by using monoclonal antibody of TP and FⅧ-RA.The correlation of TP expression with the clinical data and MVD in tumo r stroma was analyzed.Results: The expression of TP in oral squa mous cell carcinoma was much higher than that in normal oral mucosa (P0.05).There was a positive correlation between the TP expression an d MVD(P