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BACKGROUND@#Angiogenesis is described as a complex process in which new microvessels sprout from endothelial cells of existing vasculature. This study aimed to determine whether long non-coding RNA (lncRNA) H19 induced the angiogenesis of gastric cancer (GC) and its possible mechanism.@*METHODS@#Gene expression level was determined by quantitative real-time polymerase chain reaction and western blotting. Cell counting kit-8, transwell, 5-Ethynyl-2'-deoxyuridine (EdU), colony formation assay, and human umbilical vein endothelial cells (HUVECs) angiogenesis assay as well as Matrigel plug assay were conducted to study the proliferation, migration, and angiogenesis of GC in vitro and in vivo . The binding protein of H19 was found by RNA pull-down and RNA Immunoprecipitation (RIP). High-throughput sequencing was performed and next Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to analyze the genes that are under H19 regulation. Methylated RIP (me-RIP) assay was used to investigate the sites and abundance among target mRNA. The transcription factor acted as upstream of H19 was determined through chromatin immunoprecipitation (ChIP) and luciferase assay.@*RESULTS@#In this study, we found that hypoxia-induced factor (HIF)-1α could bind to the promoter region of H19, leading to H19 overexpression. High expression of H19 was correlated with angiogenesis in GC, and H19 knocking down could inhibit cell proliferation, migration and angiogenesis. Mechanistically, the oncogenic role of H19 was achieved by binding with the N 6 -methyladenosine (m 6 A) reader YTH domain-containing family protein 1 (YTHDF1), which could recognize the m 6 A site on the 3'-untransated regions (3'-UTR) of scavenger receptor class B member 1 (SCARB1) mRNA, resulting in over-translation of SCARB1 and thus promoting the proliferation, migration, and angiogenesis of GC cells.@*CONCLUSION@#HIF-1α induced overexpression of H19 via binding with the promoter of H19, and H19 promoted GC cells proliferation, migration and angiogenesis through YTHDF1/SCARB1, which might be a beneficial target for antiangiogenic therapy for GC.
Subject(s)
Humans , Cell Line, Tumor , Cell Proliferation/genetics , Endothelial Cells/metabolism , Gene Expression Regulation , Gene Expression Regulation, Neoplastic/genetics , Hypoxia , MicroRNAs/genetics , RNA , RNA, Long Noncoding/metabolism , RNA-Binding Proteins/metabolism , Scavenger Receptors, Class B/metabolism , Stomach Neoplasms/geneticsABSTRACT
Objective@#To investigate the clinicopathological features and differential diagnosis of adamantinoma of long bone.@*Methods@#Seven cases of adamantinoma on long bone were selected at Jiangsu Province People′s Hospital from June 2012 to May 2018. Clinicopathologic details, immunohistochemical and molecular analysis were performed,and the relevant literature reviewed.@*Results@#There were 6 males and 1 female patients,age ranging from 21 to 60 years (mean 38 years). Six cases were on the right side and one case was on the left; in five cases the tumors arose from tibia, one from patella and one from humerus. Microscopically,tumour cells were mainly composed of spindle cells arranged in bundles or braids,with irregular epithelial island. Immunohistochemically,the epithelial island expressed high molecular weight cytokeratin but not CK8/18. Both epithelial and spindle components expressed vimentin. One case that was microscopically similar to intraosseous synovial sarcoma did not show SYT gene rearrangement. Clinical follow-up was available for five patients: one patient had axillary metastases seven months after operation, one patient had recurrence 34 months after surgery, 3 patients were uneventful with follow up duration from half a month to 32 months.@*Conclusion@#Adamantinoma occurring in long bones is very rare. The correct diagnosis requires adequate sample selection, careful morphologic observation, immunohistochemistry and molecular genetics.
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Objective@#To evaluate the concordance of PD-L1 expression in various tissues using antibodies 28-8 and SP263 on their respective detection platforms.@*Methods@#Three hundred seventy four specimens of surgical resection of pulmonary diseases in the First Affiliated Hospital of Nanjing Medical University from January 1, 2012 to January 31, 2017 were collected. Totally 374 cases were tested for PD-L1 expression using the two antibodies, 28-8 and SP263, by respective detection platforms (Dako and Ventana). Finally, 336 cases were used for further evaluation, and the results were statistically analyzed for concordance.@*Results@#For non-small cell lung carcinoma (NSCLC), the positive rate of PD-L1 was 57.5% (177/308) using SP263, and 57.5% (177/308) using 28-8 antibody. The correlation coefficient was 0.97 (P<0.01). The positive rate of both benign lung diseases and paracancerous tissues was about 10.7% (3/28), and the positive concordance rate was 100.0%. The distribution of both antibodies was also relatively consistent.@*Conclusions@#The expression levels of 28-8 and SP263 antibodies in NSCLC and other tissues are relatively consistent, suggesting both antibodies may be complementary and substitute for each other, which may be useful in guiding clinical management.
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Objective@#To study the pathological features, immunophenotypes, differential diagnoses and prognostic parameters of collecting duct carcinoma of the kidney (CDC).@*Methods@#Clinical imaging, histopathology, immunohistochemistry, and survival data of 10 patients at First Affiliated Hospital of Nanjing Medical University from January 2009 to August 2017 were retrospectively analyzed along with a review of literatures.@*Results@#The clinical symptoms of CDC were not specific, and image examinations showed space-occupying mass lesions. Tumors were mainly located in renal medulla with grey and firm cut face and the presence of focal hemorrhage and necrosis. Microscopically, there were predominant tubular or tubular-papillary structures with associated focal sarcomatoid areas, desmoplastic stromal reaction and lymphoplasmacytic cells infiltration. Tumor cells had marked cytological atypia with high grade nuclei, conspicuous nucleolus and numerous mitoses. Immunohistochemically, tumor cells were strongly positive for CK19, E-cadherin, vimentin, HCK, CK7 and PAX8. The main treatment was radical nephrectomy in the patients. Seven cases died of CDC with median survival of 10 months.@*Conclusions@#CDC is a rare, highly aggressive malignancy of kidney with poor prognosis. Definitive diagnosis should be made by histology and immunohistochemistry. Differential diagnoses include papillary renal cell carcinoma(type Ⅱ), renal medullary carcinoma, infiltrating high grade urothelial carcinoma, renal pelvis adenocarcinoma and metastatic adenocarcinomas.
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Objective@#To investigate the relationship between PD-L1 expression and the clinicopathologic features and prognosis in triple-negative breast carcinomas (TNBC).@*Methods@#All 142 cases of TNBC were collected from the First Affiliated Hospital of Nanjing Medical University from February 2011 to December 2014, and the surgical excision or biopsy specimens from patients without chemotherapy and radiotherapy were included. Histopathologic analysis of stromal tumor infiltrating lymphocyte (sTIL) was performed on HE sections, and PD-L1 immunohistochemical staining was done with MaxVision.@*Results@#The PD-L1 expression rate was 34.5% (49/142) in tumor cells, and was 62.0% (88/142) in sTIL. The PD-L1 expression in tumor cells was positively correlated with tumor size (r=0.181, P=0.031), Ki-67 index (r=0.211, P=0.012), sTIL (r=0.380, P<0.01) and PD-L1 expression in sTIL (r=0.447, P<0.01). The PD-L1 expression in sTIL was positively correlated with tumor grade (r=0.215, P=0.01), Ki-67 index (r=0.253, P=0.002) and sTIL (r=0.370, P<0.01). The high stromal CD8+ /FOXP3+ ratio was significantly associated with improved overall survival (χ2=4.186, P=0.041). The high percentage of sTIL was significantly associated with improved overall survival (χ2=12.427, P<0.01) and progression-free survival (χ2=4.057, P=0.044).@*Conclusions@#In TNBC, PD-L1 expression is positively correlated with Ki-67 and sTIL; the stromal CD8+ /FOXP3+ ratio and sTIL are significantly associated with prognosis. The PD-L1 expression, stromal CD8+ /FOXP3+ ratio and sTIL are biologically important in TNBC, and all these correlative factors are important potential parameters in assessing immunotherapy for TNBC.
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Objective@#To evaluate the relationship between visceral pleural invasion (VPI) and other clinicopathological features in lung adenocarcinoma with tumor size ≤3 cm, and to investigate the impact of VPI on the patients′ prognosis.@*Methods@#The clinical and pathological features were retrospectively reviewed in 231 cases of lung adenocarcinoma with the largest diameter of tumor ≤3 cm, following complete resection and systemic lymphadenectomy. VPI was divided into three grades, PL0, PL1 and PL2 according to modified Hammar classification for lung cancer upon elastic fiber staining. Survival analysis was performed by Kaplan-Meier method, and the risk factors for prognosis were explored by Cox proportional hazards model. Patient prognosis was evaluated by progression-free survival (PFS) and overall survival (OS).@*Results@#In all 231 cases, the number of patients with VPI was 70 (30.3%), of which 61 cases were PL1 and 9 cases were PL2. The remaining 161 cases (69.7%) had no VPI (PL0). The tumor size (P=0.003), histological grade (P<0.01), the presence of solid component (P=0.001) and micropapillary component (P=0.009), N stage (P<0.01) and TNM stage (P<0.01) were significantly correlated with VPI. Patients with VPI had significantly shorter PFS and OS than those without VPI (P<0.01). There were significant differences in PFS and OS between patients with different VPI levels (P<0.01). Cox multivariate regression analysis showed that VPI was not an independent prognostic factor, whereas PL2 was an independent prognostic factor for PFS (P=0.007), but not an independent prognostic factor for OS (P=0.052).@*Conclusions@#For patients with lung adenocarcinoma of tumor size ≤3 cm, VPI is related to poor prognosis; However, only PL2 is an independent prognostic factor for PFS. It may be not necessary to separate PL0 and PL1 status in smaller lung adenocarcinomas. Therefore, the definition of VPI may need further modification through large cohort studies.
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Objective@#To study the clinicopathologic, immunohistochemical features, differential diagnoses and prognosis of mammary microglandular adenosis with carcinoma (MGACA) with micropapillary pattern.@*Methods@#Five cases of MGACA were collected from 2010 to 2016 and reviewed for their clinical, histologic features and outcome.EnVision method were done for S-100 protein, cytokeratin (CK), p63, Calponin, smooth muscle myosin heavy chain (SMMHC), PR, ER and HER2.@*Results@#Histologically, microglandular adenosis(MGA), atypical MGA (AMGA) and invasive carcinoma were seen in all five cases of MGACA. The invasive component was metaplastic carcinoma in one case and ductal in four cases. All epithelial cells were S-100 and CK positive in MGA, AMGA and invasive carcinoma. p63, Calponin and SMMHC negativity confirmed the lack of a myoepithelial cell layer in MGA, AMGA and MGACA. PR was weakly focally positive in one case, but ER and HER2 were negative in all cases (four cases were triple negative). Ki-67 index was 20% to 40%. Laminin and collagen Ⅳ staining showed the presence of basement membrane in MGA and AMGA, except MGACA. The follow-up time ranged from 3 months to 6 years, and all patients were alive without recurrence or distant metastasis.@*Conclusions@#MGACA is a rare tumor with distinct morphological and IHC features. Compared to most triple-negative breast cancers, MGACA seems to have a relatively favorable outcome.
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Objective To analyze the clinical prevalence,distributed characteristic of different ages,clinical characteristics and pathogenic factors of chronic abdominal pain in children.Methods A database in which outpa-tient and inpatient of abdominal pain during 2 -14 years old were collected from January 2011 to December 2015 was established by utilizing HIS system.A statistical analysis was made in age,sex,onset time,time of duration,mesenteric lymph node status and surgical situation.Results A total of 13 256 times abdominalgia were enrolled from January 2011 to December 2015.7 390 patients were diagnosed as unexplained abdominal pain,including 1 005 patients (13.59%)were diagnosed as chronic abdominal pain.A male -to -female ratio was 1.06:1.The average age was 6 years(ranged 2 -14 years).The average age of the boys was (6.02 ±2.87)years,which of the girls was (5.93 ± 2.79)years,there was no statistically significant difference between them(t =0.47,P =0.63).The peak age of chro-nic abdominal pain in children was mainly from 3 to 7 years old.The incidence decreased with age increased.The average time of duration was (16.70 ±11.69)months,that of the boys was (17.39 ±12.12)months,and that of the girls was (15.96 ±11.19)months,there was statistically significant difference between them(t =1.93,P =0.05). Mesenteric lymphadenectasis was detected in 731 patients(72.74%).The age constituent ratio decreased with age increased.The peak age of the prevalence coincided with peak age of the mesenteric lymphadenectasis.21 patients underwent surgical procedures,organic lesions accounted for 2.08%.Conclusion The peak age of the prevalence of chronic abdominal pain in children is mainly from 3 to 7 years old.Potential organic causes are rarely linked to chronic abdominal pain in children.Most of them are functional abdominal pain.The appendix and mesenteric lymphadenecta-sis might play an important role in children with chronic abdominal pain.The therapeutic aim of CAP in children is to make the children back to their normal life by exclude the organic causes and relieve their pain.The natural history of chronic abdominal pain suggests that symptoms remit spontaneously with increasing age.
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<p><b>OBJECTIVE</b>To study the clinicopathologic features and differential diagnosis of adenoid cystic carcinoma in the esophagus.</p><p><b>METHODS</b>Ten cases of primary adenoid cystic carcinoma of the esophagus were retrieved from the archival file. The clinicopathologic and immunohistochemical features were studied. The differential diagnosis was analyzed.</p><p><b>RESULTS</b>The male-to-female ratio was 9: 1. The age of patients ranged from 59 to 76 years. There were 4 cases with tumor located in mid esophagus, 4 cases with tumor located in mid to lower esophagus and the remaining 2 cases in lower esophagus. Low-power histologic examination showed mainly expansive growth pattern, with cribriform, solid and focal tubular architectures identified. The tumor cells showed nuclear hyperchromasia. Both ductal and myoepithelial differentiation was demonstrated. The stroma showed myxoid degeneration in areas. Comedo-type necrosis was observed in 8 cases and moderate to severe squamous dysplasia was present in one case. Three cases showed focal areas of squamous cell carcinoma. Immunohistochemical study showed that the tumor cells were positive for p63 (10/10), CD117 (10/10) and S-100 protein (9/10). There was focal staining for calponin (2/10) and smooth muscle actin (2/10). The ductal structures expressed CK7 (10/10).</p><p><b>CONCLUSIONS</b>Adenoid cystic carcinoma of the esophagus demonstrates unique morphologic features with expression of S-100 protein and consistent expression of CD117. The above characteristics help to distinguish this entity from basaloid squamous cell carcinoma, mucoepidermoid carcinoma and small cell carcinoma of the esophagus.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Calcium-Binding Proteins , Carcinoma, Adenoid Cystic , Chemistry , Pathology , Carcinoma, Small Cell , Chemistry , Pathology , Carcinoma, Squamous Cell , Chemistry , Pathology , Esophageal Neoplasms , Chemistry , Pathology , Immunohistochemistry , Microfilament Proteins , S100 ProteinsABSTRACT
Purpose To evaluate the application of fluorescence in situ hybridization ( FISH) in detection of EWSR1 gene translocation in formalin-fixed paraffin-embedded tissue samples of Ewing family tumor ( EFT) . Methods Four cases of EFT were collected and their clinical pathological features were obsered. Interphase FISH was carried out in paraffin-embedded tissue of EFT cases, using a EWSR1 dual colar break-apart probe. Fifteen cases of other soft tissue tumor were selected as negative control. Results Translocation of EWSR1 was detected in four EFT cases, which may be a adjuvantly diagnositic value for the diagnosis of atypical cases. Conclu-sions FISH may serve as an adjunctive diagnostic tool in problematic cases of EFT, however, FISH results should be interpreted con-cerning clinical pathological features, morphological patterns and immunohistological results.
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A 21-year-old male was hospitalized for recurrent swelling of lower limbs (lymphedema) for 1 year and worsening of it for 1 week.Physical examination revealed several smooth,firm enlarged lymph nodes of the neck,groin without apparent tenderness measuring about 1 cm in diameter.Cardiac and pulmonary auscultation showed no obvious abnormality.The abdomen was soft on palpation without tenderness or rebound tenderness.Skin examination revealed swelling of both lower limbs,especially the left lower limb,as well as scattered irregularly sized,dark erythematous patches with a wood-like consistency on the swollen lower limbs,with high temperature but no tenderness.Elevated peripheral eosinophil count was observed before and after admission,with the eosinophil percentage higher than 70％.Vascular ultrasonography showed thrombosis in the right anterior tibial artery,left dorsal artery of foot and lower portion of the left great saphenous vein.Multiple enlarged lymph nodes were found by computed tomography in the mediastinal,bilateral axillary,retroperitoneal regions and around the abdominal aorta.Lymph node and bone marrow biopsies showed eosinophilia.Histopathology of lesions on the extensor aspect of the left medial thigh and left lateral malleolus showed massive eosinophilic infiltration and lymphatic dilation in the dermis,as well as eosinophil emboli in some lumens.The FIP1L1-PDGFRA fusion gene was undetected.A diagnosis of idiopathic hypereosinophilic syndrome was finally made.The symptoms rapidly regressed after glucocorticoid treatment.
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<p><b>OBJECTIVE</b>To study the clinical and histopathologic features of metanephric adenoma (MA).</p><p><b>METHODS</b>Eight cases of recently diagnosed MA were retrieved from archival file. Immunohistochemical study was carried out. The clinical characteristics, pathologic parameters, differential diagnosis, treatment options and prognosis of MA were analyzed, with literature review.</p><p><b>RESULTS</b>The patients included 6 females and 2 males. The age of patients ranged from 12 to 70 years (mean=43.6 years). Eight cases were located in renal cortex and showed well-defined borders. Histologically, the tumor was composed of tubules lined by small basophilic cells and embedded in an edematous stroma. Papillary structures and psammoma bodies were focally seen. Immunohistochemical study showed that the tumor cells were positive for PAX2 and vimentin in all the 8 cases. WT-1 was positive in 2 cases, focal and weak in 5 cases, and negative in 1 case. CK-Pan was positive in 3 cases. CK7 staining was mostly negative, with focal and weak positivity only in 1 case. The proliferative index, as highlighted by Ki-67 staining, was less than 2% in 7 cases and focally around 5% in 1 case. The expressions of CK20, CD10, RCC, epithelial membrane antigen, CD56, synaptophysin and chromogranin A were negative. Follow-up information from 7 to 57 months was available in all patients; and none of them developed local recurrence or distant metastasis.</p><p><b>CONCLUSIONS</b>The diagnosis of MA relies primarily on thorough histologic examination and immunohistochemical study (vimentin and PAX2 positive, WT-1 focally and weakly positive in some cases, and low proliferative index). Correlation with clinical and radiologic findings would also be helpful.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Adenoma , Diagnostic Imaging , Metabolism , Pathology , General Surgery , Biomarkers, Tumor , Metabolism , Carcinoma, Renal Cell , Metabolism , Pathology , Diagnosis, Differential , Follow-Up Studies , Kidney Neoplasms , Diagnostic Imaging , Metabolism , Pathology , General Surgery , Nephrectomy , Methods , PAX2 Transcription Factor , Metabolism , Tomography, X-Ray Computed , Vimentin , Metabolism , WT1 Proteins , Metabolism , Wilms Tumor , PathologyABSTRACT
Objective To examine the expression of CGRP in congenital pseudarthrosis of tibia(CPT) in order to find the pathogenesis of CPT.Methods Periosteum and bones from CPT patients were collected as experimental group.Immunohistochemistry stain was applied to determine the differences of the expression of CGRP in two groups.Results CGRP was located at vessel wall of periosteum and intracytoplasm of osteoblasts and osteoclasts in bones,its expression was significantly less in periosteum and bones of CPT than that in control group(P