Cytojournal最新文献

Objective: In recent years, several publications have described the use of ultrasound-guided fine-needle aspiration (FNA) by cytopathologists to achieve better diagnostic accuracy. Some cytopathologists enroll in courses to learn and apply ultrasound (US) guidance themselves. However, no standard procedure has been established that cytopathologists can follow to perform US for FNA. Alternatively, FNA can be a useful tool when cytopathologists collaborate with radiologists. Here, we aimed to evaluate the diagnostic accuracy of FNA for non-thyroidal head-and-neck masses retrieved by a cytopathologist with US guidance provided by a radiologist.

Material and methods: The FNA results for non-thyroidal head-and-neck masses at a private clinic using the Scandinavian FNA model with radiologist‒cytopathologist collaboration were compared with the histopathology results.

Results: In all, 1890 patients who underwent FNA were identified, among whom 1435 (76%) also had histopathological results. Non-cystic lesions were obtained from lymph nodes (LNs), salivary glands, and soft tissue, while the other lesions were cystic in nature. For FNA, the accuracy was 99.4%, the sensitivity was 99.6%, the specificity was 99.3%, the positive predictive value was 99.3%, and the negative predictive value was 99.6%. No FNA results were non-diagnostic. Surgical follow-up revealed that only eight of the 1435 assessments (0.5%), all performed for LN lesions, yielded false-negative or false-positive results.

Conclusion: The present study is based on single-center observations. The use of FNA, when performed by a specialized cytopathologist and with US assistance from a radiologist, produces accurate results and sufficient material for analysis, especially for LNs in extrathyroidal head-and-neck lesions. This study also reveals that the technique is a low-cost and effective process. The way in which FNA is presented here indicates that this procedure would be useful and ideal for any health service.

Objective: The Japanese System for Reporting Thyroid Cytopathology (JSRTC) does not include the risks of malignancies (ROMs) or recommended clinical management. This multi-institutional study aimed to determine the frequency, re-aspiration rate, resection rate, ROM, and clinical management options in seven different categories.

Material and methods: For 15,495 cases of thyroid fine-needle aspiration performed at seven Japanese institutions without molecular testing, the frequency, re-aspiration rate, resection rate, ROM, and clinical management options of each diagnostic category were examined. The categorization was based on JSRTC, and cases were subdivided into those with nuclear atypia and other subtypes for undetermined significance.

Results: Re-aspiration of unsatisfactory and undermined significance diagnostic categories was mainly performed for cases of suspected malignancy on ultrasound. The median re-aspiration rate of cyst fluid nodules was 4.9%, which was significantly different from that (17.8%) of unsatisfactory cases (P < 0.05). The resected ROMs for nodules that were suspicious for malignancy and malignant were 94.2% and 99.6%, respectively. The low resection rates of nodules that were suspicious for malignancy (77.8%) and malignant (70.8%) could be attributed to active surveillance for low-risk papillary microcarcinoma. The overall ROMs of unsatisfactory, cyst fluid, benign, undetermined significance, and follicular neoplasms were 4.5%, 0.4%, 0.7%, 16.7%, and 11.4%, respectively. In the subtype of undetermined significance, the overall ROM of nuclear atypia (27.6%) was higher than that of the others (6.7%).

Conclusion: Overall, this study determines the frequency, ROM, and recommended clinical management for thyroid cytopathology in Japan. These results were different from those proposed by the Bethesda System for Reporting Thyroid Cytopathology. In the future, our results will be helpful in the revision of JSRTC and will contribute to improving the outcomes among Japanese patients with thyroid nodules.

Objective: Endometrial cancer (EC) ranks among the most prevalent malignant tumors affecting women, with metastasis and dissemination as the major contributors to poor prognosis. This study explores the involvement of forkhead box protein P2 (FOXP2) in EC cell invasion and migration, which is mediated through the activation of myosin light-chain kinase (MYLK).

Material and methods: Bioinformatic analysis was conducted to determine whether FOXP2 is expressed in EC. FOXP2 overexpression was achieved using a FOXP2 overexpression vector (oeFOXP2), and negative control (NC) was used for cell transfection. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine, enzyme-linked immunosorbent assay, colony formation, wound healing, and Transwell assay were used to assess the capabilities of cell viability, invasion, migration, and proliferation. Western blot and quantitative real-time polymerase chain reaction (qRTPCR) analysis were used to measure the expression levels of proteins linked to the epithelial-mesenchymal transition. The correlation between FOXP2 and MYLK was analyzed using bioinformatics and validated by Western blot and qRT-PCR analysis. The MYLK-specific inhibitor ML-7 was employed to study the impact of MYLK-mediated FOXP2 on regulating the malignant biological processes of EC.

Results: The oeFOXP2 group of EC cells exhibited a significant decrease in cell viability, colony formation, migration rate, and metastatic cell count compared with the NC group (P < 0.05). FOXP2 overexpression markedly increased caspase-3, caspase-8, caspase-9 activity (P < 0.05). Significant changes were detected in the expression of epithelial-mesenchymal transition marker proteins, with vimentin and N-cadherin expression noticeably declining and E-cadherin expression sharply rising (P < 0.05). The addition of the MYLK-specific inhibitor ML-7 reversed the effect of FOXP2 overexpression on the invasion and migration of EC cells.

Conclusion: FOXP2 suppresses the proliferation, invasion, and migration of EC cells through the activation of MYLK.

Objective: Concurrent chemotherapy and radiotherapy (CCRT) has been applied as a therapeutic modality for cervical squamous cell carcinoma (CESC). Our aim is to investigate the potential marker(s) of the efficacy of CCRT in CESC.

Material and methods: Potential candidates predictive of the efficacy of CCRT in CESC were identified. Differentially expressed genes (DEGs) were screened, followed by performing functional enrichment analyses. CCRT-related biomarkers were identified. In addition, the CIBERSORT algorithm was employed to determine the immune cell infiltration. Immune cell subsets from donors and specific cytokines were evaluated, and the biological functions of CESC cells following cisplatin treatment or coculture with M2 macrophages were explored.

Results: A total of 56 DEGs were singled out. These DEGs were enriched in pathways relevant to CESC and CCRT. They were narrowed down to eight CCRT-related biomarkers with good predictive values. Notably, most of the biomarkers were negatively correlated with M2 macrophages (P < 0.05), and regulator of G-protein signaling 2 (RGS2) exhibited low expression in CESC (P < 0.05). Flow cytometry results revealed that patients with CCRT-resistant CESC had high percentages of M2 macrophages, CD4 T cells, regulatory T cells and T helper 2 cells but low percentages of T helper 1 cells, and T helper 17 cells, M1 macrophages, and CD8 T cells (P < 0.05). Aside from interleukin (IL4) and IL-10, the remaining specific cytokines exhibited low expression in patients with CCRT-resistant CESC (P < 0.05). Furthermore, the cell cycle progression and metastasis of CESC cells were evidently promoted by M2 macrophages but were suppressed by cisplatin intervention (P < 0.05). Moreover, in CESC cells, cisplatin repressed the levels of IL-4 and IL-10 yet boosted those of the remaining cytokines, whereas M2 macrophages had the opposite effects (P < 0.05). RGS2 silencing promoted the phosphorylation of phosphatidylinositol 3-kinase/protein kinase B/transcriptional signal transducer and activator 6 in macrophages, whereas RGS2 overexpression had the opposite effect (P < 0.05).

Conclusion: This study interpreted and explored the possible predictive values of RGS2 in the efficacy of CCRT in CESC. It may provide other insights for the management of CESC.

Objective: PDZ domain containing 1-interacting protein 1 (PDZK1IP1) is commonly overexpressed in a wide variety of cancer. Hence, the objective of the present study is to ascertain the influences of PDZK1IP1 on colorectal carcinoma (CRC) development.

Material and methods: PDZK1IP1 expression was tested through reverse transcription-quantitative polymerase chain reaction and Western blot analysis, and its correlation with prognosis was analyzed using the GEPIA website. Small interfering RNA against PDZK1IP1 was adopted to downregulate PDZK1IP1 expression in CRC cells. The effects of PDZK1IP1 on cell growth were ascertained using colony formation and CCK-8 tests, and CRC cell apoptosis was analyzed through flow cytometry. Cell migration capability and invasiveness were measured using Matrigel Transwell and scratch-healing assays.

Results: PDZK1IP1 was highly expressed in the CRC tissues (P < 0.001) and cells (P < 0.05), and its knockdown restrained cell growth (P < 0.05), migratory potential (P < 0.01), and invasive capacities (P < 0.001) and accelerated cell apoptosis (P < 0.001). Mechanically, PDZK1IP1 silencing blocked CRC progression by inactivating the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of the rapamycin pathway.

Conclusion: PDZK1IP1 contributes to the oncogenesis of CRC. This finding provides a basis for the diagnosis, treatment, and prevention of CRC.

Objective: This study aims to investigate the role of fat mass and obesity-associated protein (FTO) in renal clear cell carcinoma (RCC), particularly its regulatory effects on glycolysis, cell proliferation, and sirtuin 1/forkhead box O1 (SIRT1/FOXO1) signaling pathway.

Material and methods: The messenger RNA and protein expression levels of FTO in human proximal tubular epithelial cells (human kidney 2 [HK-2]) and the RCC cell line A498 were determined by quantitative reverse transcription polymerase chain reaction and Western blot. FTO expression was downregulated by FTO short hairpin RNA and overexpressed using plasmids. Glycolysis levels were assessed by measuring glucose uptake, lactate secretion, extracellular acidification rate, and adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio. The effects of FTO on cell proliferation and cell cycle were evaluated through colony formation assays, 5-ethynyl-2'-deoxyuridine (EdU) staining, and flow cytometry. The SIRT1/FOXO1 signaling pathway was analyzed through Western blot, and FOXO1 pathway inhibitor (AS1842856) was used to further explore the role of SIRT1/FOXO1 in the FTO-mediated regulation of RCC.

Results: FTO was downregulated in A498 cells compared with that in HK-2 cells. FTO downregulation markedly increased glucose uptake, lactate secretion, and the ATP/ADP ratio in A498 cells, and its overexpression inhibited these processes. FTO downregulation also promoted RCC cell proliferation, as evidenced by an increase in colony formation and the number of EdU-positive cells. Meanwhile, FTO overexpression suppressed the proliferation of these cells. Flow cytometry analysis revealed that FTO downregulation notably increased the proportion of cells in the S phase, and its overexpression increased the proportion of cells in the G0/G1 phase. Further analysis indicated that FTO downregulation activated the SIRT1/FOXO1 signaling pathway, and its overexpression inhibited this pathway. Treatment with the FOXO1 inhibitor AS1842856 significantly reversed the pro-glycolysis and pro-proliferation effects of FTO downregulation, supporting the role of the SIRT1/FOXO1 pathway in FTO-mediated regulation.

Conclusion: FTO downregulation promotes glycolysis and proliferation in RCC cells by activating the SIRT1/ FOXO1 signaling pathway. Targeting the FTO and SIRT1/FOXO1 pathway may provide potential therapeutic strategies for the treatment of RCC.

Objective: Pancreatic cancer is a major global health challenge with high mortality rates and limited therapeutic options. Fine-needle aspiration (FNA) cytology is a key diagnostic tool, but discrepancies between cytological and histological diagnoses can impact patient management. This study aims to evaluate the diagnostic accuracy of pancreatic FNA using the World Health Organization (WHO) reporting system to assess the risk of malignancy (ROM) across different diagnostic categories.

Material and methods: The WHO reporting system was employed to reclassify 122 FNAs, with 37 cases undergoing subsequent histological correlation to evaluate the ROM. The sensitivity, specificity, positive and negative predictive values, and accuracy of ROM using the WHO system were determined through statistical analyses.

Results: The discrepancy rate between cytology and histology diagnoses was 16.2%. Category 6 (malignant) showed consistent ROM values (89%), confirming its reliability in predicting malignancy. However, Categories 1, 2, and 3 had higher ROM values than previously reported, while Category 4 had a lower ROM. Factors such as small lesion size, poor cellularity, and sampling limitations contributed to diagnostic discrepancies.

Conclusion: The study offers significant insights into the cyto-histopathological correlation in pancreatic FNA, highlighting the effectiveness of the WHO reporting system in ROM assessment. Future research with larger samples is necessary to enhance the accuracy of pancreatic FNA cytology for improved patient outcomes.

Objective: Cervical cancer ranks as the fourth most prevalent cancer among women globally; it originates in the cervix and has a significant association with human papillomavirus (HPV) infection. The purpose of this study was to investigate the diagnostic utility of cell block (CB) preparations from liquid-based cytology samples in identifying cervical lesions among Turkish patients with HPV. This approach was intended to supplement conventional Pap smear tests and HPV testing.

Material and methods: A retrospective analysis was conducted on 60 HPV-positive cervical smear samples processed through the ThinPrep Pap test. CBs were prepared from liquid-based residues, stained with hematoxylin and eosin, and analyzed. Cytological diagnoses were compared with histopathological findings from colposcopy-guided biopsies. The relationships between the Pap smear, CB, and biopsy results were statistically analyzed.

Results: Pap smear cytology identified 1.6%, 16.6%, 43.3%, and 3.3% as high-grade squamous intraepithelial lesion (HSIL), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells of undetermined significance, and atypical squamous cells - HSIL cannot be excluded + LSIL, respectively. The CB evaluations classified 6.6% of the samples as cervical intraepithelial neoplasia (CIN)1, 1.6% as CIN2, and 1.6% as squamous cell carcinoma (SCC), with 78.3% deemed negative. Histopathological biopsy revealed CIN1 in 11.7%, CIN2 in 1.7%, and CIN3 in 8.3% of the patients. High concordance was observed between the Pap smear and CB diagnoses for negative and low-grade lesions, although discrepancies occurred in higher-grade lesions. HPV testing revealed 65% high-risk positivity, predominantly for HPV16 and HPV18. Significant correlations were found among HPV subtype positivity, CB, and biopsy diagnosis (P < 0.05).

Conclusion: CB preparations provide enhanced diagnostic accuracy for high-grade lesions and SCC, thus complementing Pap smear cytology and HPV testing. This approach supports their integration into the routine cervical cancer screening protocols in Türkiye. Further global, multicenter studies are recommended to validate these findings.

Objective: Pancreatic cancer is the cancer type with the highest mortality rate worldwide, and despite advances in treatment, molecular biomarkers are needed for both early diagnosis for developing targeted therapies and improving survival rates in this challenging malignancy. In our study, the contributions of programmed death-ligand 1 (PD-L1) expression to the determination of pancreatic cancer subtypes and patient prognosis and its impact on survival were investigated.

Material and methods: Paraffin-embedded tissues from 92 patients diagnosed with pancreatic cancer were included in this study. Tumor-infiltrating lymphocytes (TILs) and lymphocytes in the stromal area within the tumor borders were scored as stromal TILs; lymphocytes in tumor islands were scored as intratumoral TILs. Staining in each area was scored as a percentage, and staining with a score of 5 or more in tumor and immune cells for PD-L1 was scored as positive.

Results: After staining, a score of 5 or more with tPD-L1 staining was used to identify one patient as having micropapillary adenocarcinoma, three patients as having ductal adenocarcinoma, and four patients as having signet ring cell carcinoma. When the clinical parameters and outcomes were compared, a statistically significant difference was found between the histopathologic type of signet ring cell carcinoma and poor differentiation and positivity of PD-L1 expression (P < 0.05). Survival was significantly influenced by tumor location, histopathological subtype, degree of differentiation, PD-L1 expression, and tumor size, with tumor size being the most critical factor (P < 0.05).

Conclusion: Our findings suggest that PD-L1 positivity is notably prevalent in signet ring cell carcinoma of the pancreas and is strongly associated with poor survival outcomes. Given these results, further studies with larger patient cohorts are warranted to validate these observations and explore potential therapeutic implications.

Objective: Ischemia-reperfusion (I-R) injury in the myocardium is a considerable challenge in cardiovascular medicine, posing a severe threat to life. Given that galectin-3 possibly regulates myocardial I-R damage, this study aims to investigate the detailed mechanisms underlying galectin-3's effects on myocardial I-R injury.

Material and methods: The expression levels of galectin-3 in vivo and in vitro myocardial I-R models were determined by Western blot and quantitative real-time polymerase chain reaction. The effects of galectin-3 on inflammatory factors and oxidative stress factors in myocardial I-R were measured with an enzyme-linked immunosorbent assay, and the extent of myocardial tissue damage was assessed using hematoxylin-eosin staining. The influence of galectin-3 on peroxisome proliferator-activated receptor g (PPARg) signaling pathway-related proteins in myocardial I-R was determined by Western blot.

Results: Myocardial I-R damage was associated with increased galectin-3 expression, and the blood levels of creatine kinase-myocardial band and creatine kinase were favorably correlated with the messenger RNA levels of galectin-3 in mice with cardiac I-R damage. The inhibition of galectin-3 alleviated oxidative stress and inflammatory response, and galectin-3 promoted reactive oxygen species production in myocardial I-R cells. Furthermore, the cardiac I-R damage mouse model exhibited decreased expression of proteins linked to the PPARg signaling pathway, but galectin-3 inhibition enhanced the expression of these proteins.

Conclusion: Galectin-3 plays a crucial role in exacerbating myocardial I-R injury, and its up-regulation is associated with increased oxidative stress, inflammatory responses, and inhibition of the protective PPARg signaling pathway. The alleviation of these harmful effects by galectin-3 inhibition suggests that targeting galectin-3 is a potential therapeutic method for reducing myocardial I-R injury.