International journal of clinical and experimental pathology最新文献

Background: Myolipoma is a rare benign mesenchymal tumor composed of mature adipose tissue, smooth muscle bundles and blood vessels, which predominantly occurs in the retroperitoneum, inguinal region and abdominal wall. Primary uterine involvement is extremely uncommon, and the presence of bizarre-nucleated cells within such tumors is even rarer. The morphological features of these cells may mimic malignant neoplasms, posing great challenges for clinical and pathological diagnosis.

Methods: We report a 61-year-old female patient with imaging and ultrasonographic findings suggestive of a uterine space-occupying lesion. Histopathological examination and immunohistochemical staining were performed on the surgically resected specimen, with the detected markers including smooth muscle actin (SMA), Desmin, HMB45, Melan A, S-100 and Ki-67.

Results: Pelvic magnetic resonance imaging (MRI) revealed a well-demarcated heterogeneous signal mass in the anterior wall of the uterine corpus, consistent with the manifestations of a benign tumor containing adipose components. Gross examination showed a well-circumscribed intramural mass of the uterus with a grayish-yellow and heterogeneous cut surface. Microscopically, mature adipocytes and benign smooth muscle cells were scattered with bizarre-nucleated cells characterized by markedly enlarged and irregular nuclei; no mitotic figures or necrotic foci were identified. Immunohistochemically, the smooth muscle component showed diffuse and strong positivity for SMA and Desmin, while HMB45, Melan A and S-100 were all negative. The Ki-67 proliferation index was extremely low (<1%), confirming the diagnosis of uterine myolipoma with bizarre-nucleated cells.

Conclusion: Uterine myolipoma with bizarre-nucleated cells is an exceedingly rare benign tumor, and no recurrence or metastasis was observed during postoperative follow-up, indicating its indolent biological behavior. Accurate diagnosis requires the combination of imaging features, adequate sampling, meticulous histological evaluation and targeted immunohistochemical detection to distinguish it from leiomyosarcoma, liposarcoma and perivascular epithelioid cell tumor (PEComa).

Breast cancer exhibits a well-documented but incompletely explained predilection for the upper outer quadrant (UOQ), accounting for 45-50% of all cases, followed by the lower inner quadrant (LIQ) as the second most common site. We propose a mechanical hypothesis: chronic, repetitive mechanical stress from sexual partner-initiated breast manipulation - specifically the four-finger pinch grasp - creates sustained micro-injury and subsequent reparative proliferation preferentially targeting the UOQ, thereby increasing local mutational burden. The thumb opposes on the LIQ, offering a natural explanation for its secondary incidence pattern. This hypothesis generates specific, testable predictions, including dose-response relationships between cumulative exposure and quadrant-specific risk, as well as lateral asymmetry based on partner handedness. A large-scale epidemiological questionnaire study is proposed as the initial validation step. If confirmed, this hypothesis may transform breast cancer risk reduction into a modifiable behavioral domain.

Background: Bladder cancer (BLCA) is a common malignant tumor of the urinary system with a poor prognosis, especially in cases of invasive or advanced patients. Although mitochondrial dysfunction is associated with tumor progression, there are relatively few mitochondrial-related prognostic models for bladder cancer. The intention of study was to construct a five-gene mitochondrial-related prognostic marker for bladder cancer, and perform external validation, and then explore its association with the tumor immune microenvironment and potential immune treatment response.

Methods: Transcriptome and clinical data were obtained from TCGA and GEO databases - intersecting bladder cancer-related differentially expressed genes (BLCA-related DEGs) with the mitochondrial-related gene database (MitoCarta 3.0 genes) to find the mitochondria-related differentially expressed genes (Mitochondria-related DEGs). Construction of a prognosis model using univariate (uni), lasso, and multivariate Cox regression analyses, was used for verificaiotn in 2 gene expression profile public databases (GEO cohorts). Functional enrichment (func enrich), tumor microenvironment (tumor microenv), immune infiltration (immune infil), mutation (mut), and single-cell transcriptomic analyses were carried out.

Results: A prognosis model was created containing five genes: COX7A1, MTHFD1L, MTG1, SCO2, and ACP6. The survival rate of high-risk patients was found to be poorer compared with that of low-risk patients. The high-risk tumor stromal score was higher, the fibroblast-related characteristics were enriched, with differences in the immune pattern. Single-cell analysis found COX7A1 in endothelial cells and mast cells, MTHFD1L in T cells, and SCO2 in endothelial cells. Functional analysis associated the high-risk group with extracellular matrix remodeling, stromal activation, and changes in immune pathways. This model also has potential value in estimating the response to immunotherapy.

Conclusions: A five-gene prognosis marker related to mitochondria for bladder cancer was developed and verified. This model may become a useful tool for survival stratification of bladder cancer patients and characterization of tumor microenvironment heterogeneity.

Objectives: Overcoming chemoresistance is a major therapeutic challenge to improve patient's outcome, and lncRNAs are involved in the carcinogenesis and progression of NSCLC. Accordingly, this study was aimed to explore the roles and functions of lncRNA FENDRR in the progression and drug resistance of NSCLC.

Methods: The University of California Santa Cruz (UCSC) Xena browser was used to validate the putative profile of lncRNA FENDRR in pan-cancer tissues, whereas Kaplan-Meier analysis was conducted to assess the overall survival rate. The potential mechanism underlying cisplatin (DDP) resistance was then investigated using transfection of siRNA-FENDRR or pcDNA3.1/FENDRR in vitro and in vivo. Simultaneously, subcellular localization of FENDRR, along with targeted DiGeorge syndrome critical region 8 (DGCR8), was predicted using lncATLAS database and further ascertained by RNA immunoprecipitation, fluorescence in situ hybridization and western blotting.

Results: LncRNA FENDRR was lowly expressed in 28 types of tumor tissues, especially in A549/DDP-resistant cells and the patients with DDP resistance. LncRNA FENDRR downregulation was associated with poor survival for patients with NSCLC. Conversely, FENDRR overexpression was observed to suppress cell viability and clonogenic ability, enhance sensitivity to cisplatin in DDP-resistant NSCLC cells and simultaneously induced their apoptosis. However, FENDRR knockdown led to opposite effects on A549 cells. Furthermore, FENDRR was predominantly located in nucleus, where its overexpression suppressed tumor proliferation in A549/DDP cells by directly targeting DGCR8.

Conclusions: Taken together, these findings suggest evidence of FENDRR in the emergence of NSCLC and further reveal a key role of the FENDRR/DGCR8 axis in the progression and drug resistance in this cancer, thereby implicating a FENDRR-targeted therapeutic strategy for combating DDP resistance in NSCLC.

[This corrects the article on p. 869 in vol. 13, PMID: 32509057.].

Acute promyelocytic leukemia (APL) is characterized by a translocation t(15;17), which leads to the fusion of the promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARA) gene. This entity represents a true medical emergency due to the high risk of coagulopathy and disseminated intravascular coagulation (DIC); thus, early diagnosis is crucial to initiate treatment and achieve a better outcome. Here, we present a challenging case of APL in a 25-year-old male that mimicked classic acute myeloid leukemia (AML) based on morphologic and immunophenotypic features. Furthermore, marked myelofibrosis was identified in our patient - an unusual finding for APL. By sharing this observation, we emphasize the importance of a comprehensive approach in achieving an accurate and timely diagnosis of APL, including the integration of morphologic assessment, immunohistochemistry, flow cytometry, and molecular techniques.

Objective: This study aims to investigate the impact of P2RX5 on the clinical pathological characteristics and prognosis of endometrial carcinoma, and to explore its potential underlying mechanisms.

Methods: The clinical samples, including 150 specimens with endometrial carcinoma (Case group) and 100 endometrial samples without cancer (Control group), were collected for analyzing the amount of P2RX5 expression. Cell biology experiments were also used for exploring the effects of P2RX5 expression on biological behaviors of endometrial carcinoma.

Results: The results showed that P2RX5 expression in endometrial carcinoma tissues were significantly higher than in endometrial tissues from the control group. Additionally, expression levels showed a positive correlation with tumor size, differentiation grade, and tumor stage, with risk values of 3.57, 6.07, and 9.78, respectively. This increase in risk was statistically significant (P < 0.001). Kaplan-Meier survival analysis demonstrated that increasing P2RX5 expression was associated with lower overall survival rates (P < 0.05). Functional assays showed that knocking-down P2RX5 expression in the HEC-1B cell line significantly reduced the capacity of cell proliferation, migration, invasion, and clone formation. Following gene knockout, the rate of late apoptosis in tumor cells significantly increased (P < 0.001), while the number of cells in the S phase and G2/M phase significantly decreased (P < 0.05).

Conclusion: These findings suggest a critical role of P2RX5 in endometrial cancer progression and thereby establish the value of P2RX5 as a prognostic biomarker and provide a promising therapeutic target for endometrial cancer treatment.

Objective: To elucidate the molecular mechanisms by which endocrine-disrupting chemicals (EDCs) initiate and sustain prostate carcinogenesis, thereby establishing a mechanistic foundation for the early detection and targeted intervention of castration-resistant prostate cancer (CRPC).

Materials and methods: A total of 402 transcriptomic profiles from public GEO cohorts were integrated. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), and network toxicology were jointly applied to prioritize candidate targets. Subsequently, an explainable XGBoost-SHAP machine-learning framework was employed to distill the core gene signature. The interaction affinities between selected EDCs and the corresponding proteins were computationally validated by molecular docking, with binding free energy (ΔG) serving as the quantitative metric.

Results: Five genes - NR3C1, CALM1, MET, STAT3 and CES1 - were identified as robust diagnostic biomarkers across multiple independent cohorts (AUC > 0.90). All five exhibited high-affinity binding to representative EDCs (ΔG < -7 kcal mol^-1).

Conclusions: For the first time, a seamless "transcriptome-network toxicology-structural biology" causal chain was established. By integrating explainable artificial intelligence with structural biology, this study closes a critical knowledge gap in the systems-level mechanism linking EDC exposure to prostate cancer initiation and progression, and offers novel, actionable targets for risk stratification and precision prevention.

Objective: To investigate the mechanism of Hesperidin (Hsp) in inhibiting the proliferation and metastasis of breast cancer cell line MDA-MB-231.

Methods: The effect of Hsp on cell survival rate was analyzed using the MTT assay. The anti-migration and anti-invasion abilities of Hesperidin were evaluated using the scratch test and Transwell migration assay. The activity of matrix metalloproteinases (MMP)-2/MMP-9 was analyzed using gelatin zymography. The expression of epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, Snail, ZO-1) was detected by Western blot.

Results: Low concentrations of Hsp (2-10 μmol/L) showed no significant cytotoxicity; 20-40 μmol/L significantly reduced survival rate (P<0.01). Scratch test results showed that Hsp inhibited wound healing in a concentration-dependent manner. Transwell migration assay showed that the number of migrating cells decreased with increasing Hsp concentration. Gelatin zymography results indicated that MMP-2/MMP-9 activity decreased with increasing Hsp concentration; Western Blotting results showed that Hsp downregulated the metastasis-related proteins Vimentin and Snail and upregulated the adhesion protein ZO-1.

Conclusion: Our findings suggest that Hsp inhibits tumor cell invasion and metastasis by potentially reducing MMP-2/MMP-9 hydrolase activity, blocking extracellular matrix degradation, and reversing the EMT process (downregulating Vimentin/Snail and upregulating ZO-1). Hsp may represent a promising candidate for adjuvant therapy in breast cancer.