International journal of clinical and experimental pathology最新文献

Background: Previous studies have reported that STAT1 (Signal Transducer and Activator of Transcription 1) is associated with multiple tumor progression. This study aimed to investigate the role and related mechanisms of STAT1 in bladder cancer.

Methods: STAT1 expression in bladder cancer tissues and human bladder cancer cell lines was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The bladder cancer cell line T24 was transfected with overexpressing lentivirus targeting STAT1. Cell proliferation, invasion, and apoptosis were measured by Cell Counting Kit-8, Transwell assays, and flow cytometric analysis. Furthermore, RNA-Seq was performed to identify the downstream signaling pathways. Finally, the signaling pathway-related molecules were determined by RT-qPCR and western blot assays.

Results: The overexpression of STAT1 inhibited bladder cancer cell proliferation and invasion while enhancing apoptosis. Moreover, the overexpression of STAT1 in bladder cancer cells delayed tumor tumorigenesis in vitro. Mechanistically, RNA-Seq analysis revealed that the JAK-STAT signaling pathway was up-regulated, especially SOCS1 (suppressor of cytokine signaling 1) and SOCS3 (suppressor of cytokine signaling 3) in STAT1-sufficient cells.

Conclusions: These results indicate the potential of STAT1 as a therapeutic target in bladder cancer.

Objectives: Thyroid hormone (TH) deficiency during pregnancy may affect cardiovascular function in offspring rats. This study aimed to evaluate the effect of TH deficiency during gestation, on the electrocardiogram indices of young and middle-aged offspring of male rats.

Methods: Eight female rats were equally divided into hypothyroid and control groups. The hypothyroid mothers received 0.025% 6-propyl-2-thiouracil (PTU) in drinking water throughout pregnancy, while control mothers consumed only tap water. Following birth, male rats from each group were observed for 4 months (young age) and 12 months (middle-aged). The group known as fetal hypothyroid (FH) consisted of rats born from hypothyroid mothers. The serum T4 and TSH concentrations from mothers and newborn male rats were assayed at the end of gestation. Lead II electrocardiogram (ECG) was recorded for 5 minutes using Power Lab, AD Instruments.

Results: There was a significant rise in the P wave voltage in young FH rats, whereas, it was decreased in middle-aged control and FH rats. The voltage of QRS decreased and its duration increased in the young and middle-aged FH rats compared to the corresponding control groups. Duration and voltage of the T wave were significantly altered in the young and middle-aged FH groups. PR and QT intervals significantly increased in the young and middle-aged FH groups compared to their controls.

Conclusions: Maternal hypothyroidism affected the electrocardiogram indices of offspring rats, possibly signaling cardiovascular problems later in life.

[This retracts the article on p. 11617 in vol. 10, PMID: 31966519.].

Leukemia cutis (LC) is defined as infiltration of the skin by leukemic cells resulting in clinically recognizable cutaneous lesions. The lesions range from violaceous papules, plaques, nodules, blisters, maculopapular rash and as erythroderma. LC can precede or happen after the presentation of leukemia. Here, we report a case of Mixed phenotype Acute leukemia (MPAL) presenting as LC (erythematous & violaceous nodules) which is a rare as well as a grave combination as it carries a worse prognosis. Here, we present a case of MPAL which presented as Leukemia Cutis proven on biopsy. The paper discusses the importance of identifying LC both in a clinical and a pathological pretext as it is important to start the Chemotherapy for MPAL at the earliest for a better outcome.

Background: Urothelial carcinoma (UC) is an aggressive tumor with high recurrence rates and poses a great challenge for clinical management. Programmed death ligand-1 (PD-L1) inhibitors and human epidermal growth factor receptor 2 (HER2) blockers have been approved for the treatment of advanced urothelial carcinoma. PD-L1 and HER2 expression in UC will determine whether patients are likely to respond to these targeted treatments. This study assessed the expressions of HER2 and PD-L1 in UC at our institution and investigated their correlations with gender, tumor location (upper genitourinary (GU) tract vs. lower GU tract), tumor stage, and histologic divergent subtypes.

Design: Patients with UC who had PD-L1 or HER2 immunostains performed in the past 3 years at our institution were included in our analysis. A total of 97 cases were identified. PD-L1 and HER2 scores were provided by two experienced GU pathologists. HER2 scores were given according to the criteria used in breast cancer, while PD-L1 scores were reported as the combined positive score. We assessed correlation of the scores with the patients' gender, tumor location, tumor stage, and histologic divergent subtypes. The data for PD-L1 expression were analyzed using the Mann-Whitney U Test for gender and urinary tract location, and one-way analysis of variance (ANOVA) for stage and histology. The data for HER2 expression were analyzed using the chi-square test. For all analyses, significance was set at P<0.05.

Results: Of the 97 patients, the average age was 69 years. There were 95 patients who had previously reported HER2 results and 86 patients who had PD-L1 results. PD-L1 expression did not show a significant difference among the histological divergent subtypes (P=0.36). However, HER2 status exhibited a significant difference, with more HER2-positive cases observed in the conventional histology (P=0.008). No correlation between HER2 status and either gender or tumor stage was identified. The median PD-L1 combined positive score was significantly higher in lower urinary tract UC than upper (10 and 2, respectively; P=0.049). No significant differences were observed for gender or pathologic stage.

Conclusion: Our data suggest that HER2 is more frequently expressed in conventional UC than in divergent subtypes. Additionally, PD-L1 has a higher expression level in lower urinary tract UC compared to upper. However, PD-L1 and HER2 expression are not related to gender or tumor stage in UC.

Five cases of FISH verified BCOR rearranged high-grade endometrial stromal sarcoma were retrospectively analyzed. The patient age ranged from 33 to 65 years (median, 48.4 years). Most patients presented with irregular vaginal bleeding (3/5) and uterus mass (2/5). Only one patient developed an abdominal wall metastasis and other patients remained in good condition during the follow-up. Pathological findings revealed that the tumors exhibited morphological diversity in terms of cell shape, arrangement pattern and tumor stroma, compared to previous summarized histology of BCOR rearranged high-grade endometrial stromal sarcoma. Detailed description of such morphology changes expanded our understanding of the histology of BCOR rearranged high-grade endometrial stromal sarcoma. Due to the non-specificity of morphology in such malignancies, molecular testing is needed for confirmation in all patients.

Background: Recent evidence suggests that the tumor stem cells that are responsible for the pathogenesis of gliomas have similar properties to those of neural stem cells. We have studied two of the most consistently expressed stem cell markers in gliomas, i.e., CD133 and Nestin, and compared them with respect to p53 expression and IDH status.

Objectives: To assess the level of expression of Nestin and CD133, and identify a correlation among various grades of diffuse glioma with IDH status and expression of p53.

Materials and methods: A cross-sectional retrospective study with 102 subjects for the expression of cancer stem cell markers; CD133 and Nestin and the correlation of their expression with that of p53 and IDH1 status in adult diffuse glioma. The study was conducted in the Departments of Pathology and Neurosurgery. The expression was assessed by immunohistochemistry on formalin-fixed paraffin-embedded sections. The scoring of expression of CD133 and Nestin was adapted from Zhang et al. The scoring for p53 was adopted from Aruna et al. Results: The diffuse gliomas were graded based on WHO into grade II (30.3%), grade III (28.4%), and grade IV (41.3%). Among WHO grade IV, 59.4% were primary, and 40.4% were secondary glioblastomas. 73% of the diffuse gliomas were IDH mutant, and p53 showed an overall expression of 76.4%. The expression of CD133 and Nestin were compared with the increasing grades of diffuse gliomas, which, when plotted on ROC curves, had AUCs of 0.6806 and 0.6119, respectively. Their expression showed a positive correlation with the IDH status of the tumor.

Conclusions: Cancer stem cell markers CD133 and Nestin are expressed in diffuse glioma and have a higher expression with increasing WHO grade of malignancy. These cancer stem cell markers have shown significant association with the IDH-1 mutant status of diffuse gliomas. Hence, it can be inferred that diffuse gliomas with a higher expression of CD133 and Nestin have a poorer prognosis. Further, these cancer stem cell markers may be used as therapeutic targets in the future.

A case of diffuse midline glioma (DMG), H3 K27-altered, that arose in the right thalamus of a 14-year-old boy is reported. The patient died of tumor spread after a progressive clinical course of approximately 13 months. Histopathologically, the tumor consisted of a mixture of loose proliferation of stellate cells and compact fascicular growth of spindle cells showing a "piloid" feature. Aggregates of globular structures composed of entangled fine glial fibrils ("glio-fibrillary globules, GFGs") were observed. Tumor cells were immunoreactive for S-100 protein and glial fibrillary acidic protein (GFAP), and showed nuclear immunoreactivity for histone H3 K27M and loss of expression of H3 K27me3. Tumor cell nuclei were also negative for alpha-thalassemia/mental retardation syndrome X-linked protein (ATRX) and p16. Although GFGs morphologically resembled "neuropil-like islands" or "neurocytic rosettes" seen in glial or glio-neuronal tumors, they showed immunoreactivity for GFAP, but not for synaptophysin. A GFG is a unique structure that has been described in DMG, H3 K27-altered, by a few investigators. To the best of our knowledge, this structure has not previously been reported in other glial or glio-neuronal tumors. It could be added as a new feature in the histopathological variations of DMG, extending its morphological spectrum. Familiarity with this feature can help prevent misdiagnosis of DMG.

Objectives: Helicobacter pylori (H. pylori) is a globally prevalent bacterium that increases the risk of developing various gastrointestinal diseases, including gastric adenocarcinoma. This study aimed to evaluate the performances of real-time PCR assay in detecting H. pylori infection, as well as clarithromycin and levofloxacin resistance, in both stool and gastric biopsy specimens.

Methods: Stool and gastric biopsy specimens were collected from patients within one to three days post-hospitalization. All patients were analyzed for H. pylori infection and resistance to clarithromycin and levofloxacin using a real-time PCR based molecular assay.

Results: 169 patients (83 males) with a mean age of 43.6±13.1 years were included in the study. The prevalence of H. pylori was 89.9% (152/169) in stool and 90.5% (153/169) in gastric biopsy samples. The molecular diagnostics employed in this study exhibited a sensitivity of 99.3% and a specificity of 100%, resulting in a diagnostic accuracy rate of 99.6%. Resistance to clarithromycin was 36.1% (61/169) in stool and 44.4% (75/169) in gastric biopsy samples. The molecular tests for clarithromycin resistance demonstrated a sensitivity of 96.8% and a specificity of 86.8%, with an overall diagnostic accuracy of 90.5%. Furthermore, resistance to levofloxacin was 22.5% (38/169) and 26.6% (45/169) in stool and gastric biopsy samples, respectively. The molecular test demonstrated a sensitivity of 80.9% and a specificity of 94.3%, resulting in a diagnostic accuracy of 90.5%.

Conclusion: The implementation of real-time PCR-based screening for H. pylori infection and resistance to clarithromycin and levofloxacin in the stool may enhance the success rate of eradication therapy.

Cell cycle-dependent protein kinase 4/6 (CDK4/6) is a crucial kinase that regulates the cell cycle, essential for cell division and proliferation. Hence, combining CDK4/6 inhibitors with other anti-tumor drugs is a pivotal clinical strategy. This strategy can efficiently inhibit the growth and division of tumor cells, reduce the side effects, and improve the quality of life of patients by reducing the dosage of combined anticancer drugs. Furthermore, the combination therapy strategy of CDK4/6 inhibitors could ameliorate the drug resistance of combined drugs and overcome the CDK4/6 resistance caused by CDK4/6 inhibitors. Various tumor treatment strategies combined with CDK4/6 inhibitors have entered the clinical trial stage, demonstrating their substantial clinical potential. This study reviews the research progress of CDK4/6 inhibitors from 2018 to 2022, the related resistance mechanism of CDK4/6 inhibitors, and the strategy of combination medication.