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Objective@#To investigate the clinicopathologic and molecular features of the rare cribriform morular variant of papillary thyroid carcinoma (CMV-PTC).@*Methods@#The clinicopathologic data of 10 patients with CMV-PTC were retrospectively reviewed. Immunohistochemical (IHC) staining was done using LSAB method. DNA sequencing for APC were applied using Sanger method. BRAF V600E mutation was examined using ARMS method. The cytological, morphological, IHC and molecular features were analyzed.@*Results@#All patients were female at an average age of 27 years old. The tumors were mostly located in the right lobe of thyroid. Fine needle aspiration cytology was performed in three patients; two were diagnosed as suspicious for PTC and one as PTC. Nine tumors presented as solitary nodule and two as multiple nodules in both lobes. Infiltration was demonstrated in three cases. The average size was 2.6 cm. The neoplastic cells were arranged in papillary, cribriform, solid and glandular patterns, with rare or without colloid inside the lumen. The number of morula varied, ranging from zero to many. The neoplastic cells were variably enlarged, showing round, oval or spindle shape. Nuclear irregularity was identified as irregular membrane, nuclear grooves or pseudoinclusion, but no typical ground glass feature. Peculiar nuclear clearing could be observed in the morular cells. IHC staining showed the neoplastic cells were negative for thyroglobulin and p63, but positive for TTF1, cytokeratin 19 and estrogen receptor. Diffuse staining with cytokeratin was seen in the neoplastic cells and the morula. Specific cytoplasmic and nuclear staining of β-catenin was seen in the neoplastic cells but not the morula. Ki-67 proliferation index was 1%-30%. No recurrence or metastasis was observed. One patient was demonstrated to harbor both somatic and germline mutations of the APC gene, who was found to have adenomatous polyposis and her mother died of colonic carcinoma. No BRAF V600E mutation was detected.@*Conclusions@#CMV-PTC is rare and shows atypical cytological and clinicopathological features, and it is easily misdiagnosed.TG, TTF1, ER and β-catenin are specific IHC markers for CMV-PTC. The morula is negative for cytokeratin 19, in contrast to squamous metaplasia. Although CMV-PTC has indolent clinical behavior, a definite diagnosis is necessary to rule out the possibility of APC gene mutation and related extra-thyroidal neoplasm, such as FAP and Gardner syndrome.
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Objective To investigate the clinicopathological significances of LDHA/mutant p53 co-expres-sion in gliomas. Methods According to the 2016 WHO CNS,archived 68 gliomas were collected and analyzed retrospectively. The co-expression of LDHA/mutant p53 was detected by immunohistochemical staining. Results High expression of LDHA alone was always found in high grade gliomas(48.5%). Mutant p53 high expression was usually observed in glioblastomas (26.5%). There was a close relationship between co-expression of LDHA/mutant p53 in glioblastoma(27.9%,P = 0.005),or gliomas with high histological grading(27.9%,P = 0.002). Conclusions Co-expression of LDHA/mutant p53 in tumor cells might be a specific immunohistochemical pheno-type of gliomas,and may help for distinguishing glioblastoma and other high grade gliomas from low grade gliomas.
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Objective To investigate the potential pathogenesis of Focal cortical dysplasia (FCD), we performed cDNA microarray analysis to obtain gene expression profile of FCD. Methods Three FCD samples and three normal controls were enrolled. Total RNA of the brain tissues were extracted. The difference gene expressions between FCD group and control group was detected using Affymetrix gene chip. The up and down-regulated genes were confirmed by Real-time PCR. Further, the related signal pathways involved in the pathogenic mechanisms of FCD were predicted by bioinformatics. Result In FCD, two up-regulated genes C21orF2 and AU152162 and 5 down-regulated genes ENPP2, ANLN, IP6K3, UGT8, and AZGP were found. Compared the FCD samples with the normal controls , there were significantly different in all down-regulated genes (P 0.05). Using bioinformatics analysis, the ENPP2 , UGT8 , and AZGP1 protein which located in the cell membrane or secreted into the extracellular matrix may be involved in the formation of the myelin sheath and the development of the nervous system by the lipid metabolism and LPA signaling pathway. Conclusion ENPP2, UGT8 and AZGP1 may be involved in pathogenesis of FCD through the process of myelin sheath formation and LPA signal pathway , which warrants further study to know their roles in the pathogenesis of FCD.
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Objective To investigate the effect of Bcl-2 gene knockdown on apotosis , proliferation and drug sensitivity of gastric carcinoma HGC-27 cells. Methods The HGC-27 cells were divided into five groups:the untreated control group , the control siRNA group , the specific siRNA targeting Bcl-2 gene group , 5-FU treated group and the combination group (Bcl-2 siRNA and 5-FU treatment). Then flow cytometry and MTT assays were performed to detect the apoptosis and proliferation of HGC-27 cells. The cysteine protease activityand Cytochrome C release level were tested by ELISA method. Results Bcl-2 knockdown enhanced apoptosis and inhibited proliferation of HGC-27 cells. Comparedwith the 5-FU-treated group , the cell apoptosis level, activities of Caspase-3 and Caspase-9, plasma Cytochrome C were significantly increased in the combination group(P <0.01). Conclusion Bcl-2 gene knockdown induced apoptosis, inhibited cell proliferation and enhanced the drug sensitivity of 5-FU in gastric cancer cells , which might be considered as a potential therapeutic strategy forgastric carcinoma.
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<p><b>OBJECTIVE</b>To study the effect of hepatitis C virus nonstructural protein NS(3) (HCV NS3) on telomerase activity and carcinogenesis.</p><p><b>METHODS</b>Streptavidin-peroxidase (SP) conjugated method was used to detect the expression of HCV NS(3) protein in NIH3T3 cells transfected with plasmid pRcHCNS(3)-5' and pRcHCNS(3)-3'. Telomerase activity was detected by an in situ telomerase activity labeling method, telomeric repeat amplification protocol polymerase chain reaction (TRAP-PCR) and telomerase PCR enzyme linked immunosorbent assay (ELISA) technology in the transfected and non-transfected NIH3T3 cells.</p><p><b>RESULTS</b>HCV NS(3) protein was expressed in the NIH3T3 cells transfected with plasmid pRcHCNS(3)-5' expressing HCV NS(3) C-terminal deleted protein or with plasmid pRcHCNS(3)-3' expressing HCV NS(3) N-terminal deleted protein. The positive signal of HCV NS(3) protein was localized in the cytoplasm of NIH3T3 cells, and the signal intensity of the former was stronger. Telomerase activity in NIH3T3 cells transfected with plasmid pRcHCNS(3)-5' was stronger than that in NIH3T3 cells transfected with plasmid pRcHCNS(3)-3' (P < 0.01), whereas telomerase activity in NIH3T3 cells transfected with plasmid pRcCMV or untreated NIH3T3 cells was weaker than that in NIH3T3 cells transfected with plasmid pRcHCNS(3)-3' (P < 0.05). The expression level of HCV NS(3) protein was significantly correlated with the strength of telomerase activity (P < 0.05). The results obtained by in situ telomerase activity labeling corresponded to the results by telomerase PCR ELISA technology.</p><p><b>CONCLUSIONS</b>HCV NS(3) protein may activate telomerase through endogenous mechanism to induce host cell transformation. The effect of HCV NS(3) C-terminal deleted protein on telomerase activity in the host cell may be stronger than that of HCV NS(3) N-terminal deleted protein. In situ telomerase activity labeling was a reliable technology for studying pathological morphology and telomerase activity in tissues and cells.</p>