International journal of clinical and experimental pathology最新文献

Background: Semaphorin4F (Sema4F) is a member of the semaphorin family and exhibits important regulatory functions in cancer biology. We aimed to explore the prognostic value and biologic function of Sema4F in gastric cancer (GC) through clinical data, laboratory studies, and bioinformatic methods.

Methods: We investigated Sema4F-related data and the prognostic values of patients with GC based on several databases, including Tumor Immune Estimation Resource (TIMER), the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), The University Of Alabama At Birmingham Cancer Data Analysis Portal (UALCAN) and Kaplan-Meier Plotter. We detected the expression of Sema4F in cell lines and tumor tissues by reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry. The prognostic value of Sema4F expression on patient overall survival was analyzed retrospectively using Kaplan-Meier survival and Cox regression analyses. Moreover, we used Kyoto encyclopedia of genes and genomes (KEGG), Gene Ontology (GO) and Gene-set enrichment analysis (GSEA) analyses to explore the relevant pathways of Sema4F in GC.

Results: The expression of Sema4F was markedly increased in cancer tissues and cancer cell lines. Furthermore, high Sema4F expression was positively associated with various clinicopathologic data and independently predicted poor prognosis for overall survival in GC. Our functional enrichment analysis revealed that Sema4F was mainly involved in oxidative phosphorylation and tumor-related signaling pathways.

Conclusions: Sema4F may be a valuable prognostic biomarker and a novel target for gastric cancer.

Solitary fibrous tumor (SFT) of the urinary bladder has been rarely reported and malignant bladder SFT is even rarer. Here we present a case of an African-American male with SFT of the urinary bladder (intermediate risk) initially treated by cystoprostatectomy at the age of 59 years. Eight years later, he developed recurrence with widespread metastases to the liver, lungs, and abdominal cavity. He then received temozolomide and bevacizumab with good disease control. However, treatment was paused due to declining performance status. Follow-up at 1 year demonstrated growth of the metastatic lesions. Despite restarting therapy, the patient expired, 11 years after the original diagnosis. Autopsy was performed and revealed widespread metastases within the abdominal cavity (abdominal sarcomatosis) as well as liver, bilateral lung, and diaphragmatic involvement. The cause of death was determined to be metastatic SFT. A comprehensive literature review was performed. Although SFTs are commonly considered benign, a subset of SFTs of the urinary bladder behave aggressively. Risk assessment and proper follow-up for recurrence and metastasis is necessary. The patient was also found at autopsy to have two gastrointestinal stromal tumors (GISTs) in the stomach and near the gastroesophageal junction. To the best of our knowledge, this is the first reported case of a primary urinary bladder SFT resulting in death or having concurrent, multifocal GISTs, and only the second case of a bladder SFT that developed metastases after the initial diagnosis.

Uterine sarcomas are a group of rare malignant tumors of mesenchymal tissue of the uterus, and their diagnosis is often difficult because they have variable morphologies and no typical immunophenotype. This report describes a 48-year-old woman who underwent laparoscopic myomectomy and relapsed within 5 years with a large mass in the pelvic cavity. Morphologically, the tumor was composed of oval cells and small arteries, and the cells showed moderate to severe atypia. Immunohistochemical results showed that the tumor cells expressed desmin, smooth muscle actin, and h-caldesmon, which supported myogenic differentiation. They were strongly positive for Cyclin D1, estrogen receptors (ER), and estrogen receptors (PR), supporting their origin from uterine mesenchymal cells. Next-generation sequencing (NGS) revealed a GATAD2B::MMRN1 rearrangement. The patient was diagnosed with uterine sarcoma resembling high-grade endometrial mesenchymal sarcoma with a GATAD2B-MMRN1 fusion. We review the relevant literature and discuss the diagnostic and differential diagnostic points for this disease.

Objectives: The clinical, pathological, and laboratory correlates of normoblastemia in COVID-19 patients have not been adequately explored. We sought to assess the frequency of normoblastemia in COVID-19, its association with other markers of disease, as well as other clinical outcomes.

Methods: All COVID-19 patients seen at our institution with at least one automated complete blood count (aCBC) evaluation from March to May 2020 were included in this retrospective cohort analysis. Results of aCBC and tests for markers of the acute phase response performed within 5 days before the first COVID-19 positive test and 14 days after the last positive test were reviewed. We also evaluated histologic features of the reticuloendothelial system of COVID-19 decedents.

Results: Among a total of 2501 COVID-19 patients, 715 (28.6%) were found to have normoblastemia. Patients with this abnormality had significantly higher (median, (1^st quartile, 3^rd quartile) WBC (15.7 (11.2, 23.1) u/L vs. 8.3 (6.2, 11.5) u/L), absolute neutrophil count (7.0 (5.1, 10.1) u/L vs. 5.1 (3.7, 7.3) u/L), immature granulocyte percentage (0.8 (0.5, 1.3)% vs. 0.5 (0.3, 0.8)%), ESR (76.0 (60.5, 100.0) mm/hr vs. 66.0 (45.0, 87.0) mm/hr), ferritin (1404.5 (645.0, 2871.0) ng/mL vs. 672.7 (313.4, 1348.0) ng/mL), INR (1.4 (1.2, 1.7) vs. 1.2 (1.1, 1.3)), D-dimer (8.2 (2.8, 20.0) ug/mL FEU vs. 1.5 (0.8, 3.7) µg/mL FEU), and IL-6 (216.6 (77.7, 315.0) pg/mL vs. 54.3 (23.2, 127.8) pg/mL) levels, and lower hemoglobin (12.5 (10.7, 14.2) g/dL vs. 13.2 (11.8, 14.6) g/dL) and absolute lymphocyte count (1.0 (0.7, 1.3) u/L vs. 1.1 (0.8, 1.5) u/L). The incidence of intubation and ventilation support (61.3% (65/106) vs. 10.5% (31/263)) and mortality rates (37.9%, 271/715 vs. 11.8%, 210/1786), were higher in normoblastemic patients. Multivariable logistic regression revealed normoblastemia to be an independent predictive biomarker of short-term mortality in COVID-19.

Conclusion: Normoblastemia in COVID-19 is associated with markers of severe disease, extramedullary erythropoiesis, and adverse clinical outcome.

Objective: Whether there is a correlation between zinc-finger E-box-binding homolog 1 (ZEB1) and Yes-associated protein 1 (YAP1) with clinical outcome in gliomas remains unclear. Hence, this study aimed to investigate the effects of ZEB1 and YAP1 on the prognosis of human gliomas and its relationship with the isocitrate dehydrogenase 1 (IDH1) gene state.

Methods: Immunohistochemical staining was used to record the expression levels of ZEB1, YAP1, and p-YAP1 in 122 cases of low-grade glioma (LGGs) and 69 cases of glioblastoma (GBMs). The correlations of ZEB1 and YAP1 with pathological data were determined by Pearson's Chi-square test. Spearman correlation analysis was then used for analyzing the relationship among YAP1, ZEB1, and IDH1 gene status. The effects of ZEB1 and YAP1 on prognosis were investigated through survival analysis.

Results: We detected high ZEB1 expression levels in 29 LGGs (23.8%) and 39 GBMs (56.5%), and high YAP1 expression levels in 22 LGGs (18.0%) and 44 of GBM (63.8%). These results revealed that the protein expression levels of ZEB1 and YAP1 were higher in GBM (P < 0.001). There was a significantly positive correlation between ZEB1 and YAP1 (P < 0.001; r = 0.533). High ZEB1 expression was related to tumor grade (P < 0.001) and Ki-67 (P = 0.0037). YAP1 overexpression was correlated with Ki-67 (P < 0.001), P53 (P = 0.009), tumor grade (P < 0.001), and tumor location (P = 0.018). Patients with ZEB1 and YAP1 high expression had worse overall survival (OS) (P < 0.001). The multivariate analysis showed that YAP1 was an independent prognostic factor for OS. In the LGG group, worse OS were observed in glioma patients with elevated YAP1 expression level. Spearman correlation analysis revealed no association between ZEB1 expression and IDH1 state (P = 0.360; r = -0.084), and YAP1 expression had a negative correlation with IDH1 mutation (P < 0.001, r = -0.364).

Conclusions: Our study showed that ZEB1 and YAP1 were significantly activated in GBM, and patients with high ZEB1 and YAP1 expression had worse OS. ZEB1 expression was significantly correlated with YAP1 in glioma. ZEB1 and YAP1 coexpression may serve as a useful prognostic biomarker for glioma, and aberrant YAP1 expression may be associated with IDH1 gene state.

Objective: Folic acid (FA) may contribute to the development of gestational diabetes mellitus (GDM), but available studies are inconsistent. We studied the genotype distribution and allele frequencies of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C, and methionine synthase reductase (MTRR) A66G polymorphisms in pregnant Chinese women and compared the effects of individualized and traditional FA supplementation on GDM.

Methods: In this retrospective study, genotype distribution and allele frequencies in 968 pregnant women were tested. FA metabolism was tested by dividing patients into four groups, each of which was supplemented with different doses of FA at different times. Pregnancy complications were followed up and compared to 1940 pregnant women traditionally supplemented with FA in the same hospital as a control group.

Results: The allele frequencies were 63.3% (C) and 36.7% (T) for MTHFR C677T, 79.3% (A) and 20.7% (C) for MTHFR A1298C and 75.0% (A) and 25.0% (G) for MTRR A66G. The incidence of GDM after FA supplementation was significantly lower in the case group compared to the control group, especially in high-risk pregnancies.

Conclusion: Using genetic polymorphisms to elucidate FA metabolism in pregnant women and providing appropriate FA supplementation can be effective in reducing GDM, especially in high-risk groups.

Objective: Histone deacetylases (HDACs) not only regulate histone acetylation but also participate in many pathophysiologic processes, especially the development of cancer, including breast cancer. However, whether Histone deacetylase 11 can influence breast cancer is still unknown. This study investigated the relationship between HDAC11 expression in breast cancers and clinicopathologic parameters, and used small interference RNA (siRNA) to determine the biological behavioural changes after knockdown of HDAC11.

Methods: Immunohistochemical (IHC) staining was employed to detect the expression of HDAC11 in a tissue microarray (TMA) of 145 patients with invasive ductal breast carcinoma. Transwell and wound healing assays were employed to analyze cell invasion and migration. The proliferation ability of cells was determined by Cell Counting Kit (CCK8).

Results: The results show that the expression of HDAC11 was positively correlated with the overall survival (OS) of breast cancer patients. Specific HDAC11 knockdown enhanced MDA-MB-231 cell proliferation, migration, and invasion.

Conclusion: In conclusion, this study found that HDAC11 expression is positively correlated with the overall survival rate of patients. HDAC11 can inhibit the invasion and proliferation of breast cancer cells to a certain extent and can be used as a good prognosis marker.

[This retracts the article on p. 10666 in vol. 10, PMID: 31966410.].

Background: Colorectal cancer is the third most common cancer and the fourth leading cause of cancer deaths. Prognosis is poor. The majority of patients are diagnosed with locally advanced or metastatic disease. Increasing evidence suggests G protein subunit gamma 5 (GNG5) play key roles in several types of human cancer. The key gating mechanisms in colorectal cancer remains unkown.

Methods: In this study, pan-cancer analyses have been performed for GNG5's expression. Prognosis using The Cancer Genome Atlas and The Genotype-Tissue Expression data found that GNG5 are activated oncogenes in colorectal cancer. Noncoding RNAs play increasingly appreciated gene-regulatory roles and long noncoding RNAs contributing to GNG5 overexpression. They were identified by a combination in silico computational analyses. We identified candidate regulators controlling colon carcinoma survival analysis and correlation analysis.

Results: The SNHG4/DRAIC-let-7c-5p axis was identified as the most progressive upstream lncRNA-related pathway of GNG5 in colorectal cancer. The GNG5 level was significantly negatively correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint expression.

Conclusions: Our findings elucidated that lncRNAs-mediated downregulation of GNG5 correlated with better prognosis and tumor immune infiltration in colorectal cancer.

Objective: Detection of gene rearrangements in MYC (a family of regulator genes and proto-oncogenes) and human B-cell lymphoma 6 (BCL6) using fluorescence in situ hybridization (FISH) are important in the evaluation of lymphomas, in particular diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. Our current clinical MYC and BCL6 FISH workflow involves an overnight hybridization of probes with digital analysis using the GenASIs Scan and Analysis instrument (Applied Spectral Imaging). In order to improve assay turnaround time SureFISH probes were validated to reduce the hybridization time from 16 hours down to 1.5 hours.

Methods: Validation was a four-phase process involving initial development of the assays by testing new probes in a manual protocol, and cytogenetic studies to confirm the probe specificity, sensitivity, and localization. In the next phase, the assays were validated as a manual assay. The third phase involved development of the digital FISH assays by testing and optimizing the GenASIs Scan and Analysis instrument. In the final phase, the digital FISH assays were validated.

Results: Cytogenetic studies confirmed 100% probe sensitivity/specificity, and localization patterns. Negative reference range cutoffs calculated from 20 normal lymph nodes using the inverse of the beta cumulative probability density function (Excel BETAINV calculation) were 11% inclusive for both manual and digital MYC and BCL6 assays. There was 100% concordance between the manual and digital methods. The shortened hybridization time decreased the overall workflow time by 14.5 hours.

Conclusions: This study validates the use of the SureFISH MYC and BCL6 probes on formalin fixed paraffin embedded (FFPE) tissue sections using a hybridization time of 1.5 hours that shortened the overall workflow by 14.5 hours. The process described also provides a standardized framework for validating digital FISH assays in the future.