International journal of clinical and experimental pathology最新文献

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.

Objective: This study aims to investigate the pathogenesis, clinical characteristics, diagnosis, treatment, and prognosis of primary thyroid lymphoma (PTL) for a better understanding of the disease and a more accurate PTL diagnosis, thereby preventing misdiagnosis and mistreatment.

Methods: The clinical manifestations, biochemical examination, ultrasound examination, imaging examination, pathologic examination, diagnosis, and treatment of four PLT patients admitted to the Department of Thyroid and Breast Surgery of the Affiliated Hospital of Inner Mongolia Medical University from January 2010 to December 2020 were retrospectively analyzed.

Results: Diffuse large B-cell lymphoma (DLBCL) expressing cluster of differentiation 20 (CD20) were detected in all four PTL patients. Hashimoto's thyroiditis (HT) with increased anti-thyroglobulin antibodies (TGAb) occurred in two PTL patients, while antithyroid peroxidase autoantibody (TPOAb) was increased in three cases. All four patients underwent surgical and chemoradiotherapy treatments. Patients were without tumors during the follow-up ranging from 8 to 55 months.

Conclusion: PTL is a primary extranodal lymphoma of the thyroid and is mainly derived from B-cell non-Hodgkin's lymphoma. The pathogenesis of PTL remains unclear, but it is closely related to HT. Clinical diagnosis in this study was determined by either needle biopsy or surgical resection.

Objective: The extent of tumor regression varies widely among patients who receive neoadjuvant chemoradiotherapy (NACRT) followed by total mesorectal excision (TME) surgery. We evaluated the tumor regression grade (TRG) classification of patients and analyzed factors related to TRG and its value in predicting prognosis in locally advanced rectal cancer (LARC).

Methods: This study retrospectively analyzed the clinicopathologic data of 269 consecutive patients with LARC treated from February 2002 to October 2014. The grade of TRG was based on the extent of primary tumor replaced by fibrosis. Clinical characteristics and relative survival were retrospectively analyzed.

Results: There were 269 patients, among whom 67 patients (24.9%) achieved TRG0, whereas 46 patients (17.1%) showed TRG3. TRG1 and TRG2 were both found in 78 patients (29.0%). Clinicopathologic factors that were related to TRG included post-NACRT carcinoembryonic antigen (CEA) level (P=0.002), clinical T stage (P=0.022), pathologic T stage (P<0.001) and pathologic lymph node status (P=0.003). The 5-year overall survival (OS) was 74.6%, 55.1%, 47.4%, 28.3% for TRG0, TRG1, TRG2, TRG3, respectively (P<0.001). The 5-year disease-free survival (DFS) was 64.2%, 47.4%, 37.2%, 23.9% for TRG0, TRG1, TRG2, TRG3, respectively (P<0.001). Based on multivariate analysis, TRG was a significant predictor for both OS (P=0.039) and DFS (P=0.043).

Conclusion: Clinicopathologic factors such as post-NACRT CEA level, clinical T stage, pathological T stage and pathological lymph node status are significantly associated with TRG. TRG is an independent predictor of survival. Therefore, it is reasonable to include the TRG for clinicopathologic assessment.

Objectives: Diagnosis of angiomatoid fibrous histiocytoma (AFH) can be challenging due to its variable histologic features and a lack of highly sensitive and/or specific immunohistochemical markers. The utility of TLE1 and BCOR as immunohistochemical markers for AFH is not known.

Methods: We examined the spectrum of histologic features of 36 AFHs, and studied the expression of both TLE1 and BCOR in AFH and its mimics by immunohistochemical staining. Positive nuclear expression was scored semiquantitatively.

Results: Both typical and unusual histologic features of AFHs were observed in this cohort. TLE1 was moderately to strongly positive in 36/36 AFHs, 4/4 synovial sarcomas, and 2/3 BCOR sarcomas; weakly positive in 4/6 inflammatory myofibroblastic tumors; negative in all dermatofibromas (n = 10), atypical fibrous histiocytomas (n = 5), myofibroma (n = 2) and juvenile xanthogranulomas (n = 5), with an overall sensitivity of 100%, and specificity of 71.4% for AFH. BCOR was moderately to strongly positive in 24/36 AFHs, 4/4 synovial sarcomas, 3/3 BCOR sarcomas, and 1/5 atypical fibrous histiocytomas; weakly positive in 10/36 AFHs; negative in the remaining tumors. The overall sensitivity and specificity of BCOR for AFH were 94.4% and 77.1%, respectively.

Conclusions: TLE1 is a highly sensitive immunohistochemical marker for AFH.