With the in-depth promotion of precision medicine for breast cancer,pathological diagnosis has changed from traditional histological classification to a multidimensional system integrating morphology,immunohistochemistry and molecular target detection,and becoming a pivotal component in clinical treatment decision-making.Currently,the pathological diagnosis of breast cancer necessitates continuous optimization,including standardizing the interpretation of HER2-low expression,promoting the upfront detection for key targets,refining the structure of pathological reports,and further enhancing collaboration with clinical teams.These efforts aim to better meet the demands of precision treatment and provide patients with superior diagnostic support.Based on the clinical research progress and guideline consensus in recent years,this paper delves into the critical pathological hotspots in the clinical diagnosis and treatment of breast cancer,aiming to facilitate the implementation of standardized pathological diagnosis within the precision treatment framework.

HPV-independent vulvar intraepithelial neoplasia is rare and often develop vulvar squamous cell carci-noma in a short period of time or at the same time,and is the most common pre-lesion of vulvar squamous cell carcino-ma.HPV-independent vulvar intraepithelial neoplasia is significantly different in pathogenesis,pathological morpholo-gy,molecular characteristics,clinical treatment and prognosis.HPV-independent vulvar intraepithelial neoplasia is di-verse in morphology and can be divided into differentiated vulvar intraepithelial tumors and verrucous/acanthogenic in-traepithelial tumors/abnormal vulvar maturation,including TP53 gene mutant and wild type.HPV-independent vulvar intraepithelial neoplasia often occurs on the basis of chronic skin inflammation,and are easily confused with chronic dermatitis and squamous epithelial reactive hyperplasia.Correlation with the clinical,selecting appropriate immunohis-tochemical markers or molecular testing can help diagnose the disease.

Purpose To investigate the expression of bone sialoprotein(BSP)in the tissues and cells of endome-trial cancer(EC)and its effects on the proliferation and invasion of EC cells.Methods The expression of BSP was assessed by immunohistochemistry in 235 EC tissues and 88 normal endometrial tissues,and its correlation with clinico-pathological features was analyzed.Western blot was used to compare BSP levels between human endometrial carcinoma cell line(HHUA)and normal human endumetial epithelial cells(HEEC).BSP was knocked down in HHUA cells via transient transfection,and the cells were divided into blank control group and BSP-knockdown group.The effects of BSP knockdown on cell cycle,proliferation,migration,invasion,and apoptosis were evaluated using PI staining,CCK-8,scratch,Transwell,and Annexin V-FITC assays,respectively.Protein levels of TGF-β signaling pathway compo-nents were analyzed by Western blot.Results BSP expression was significantly higher in EC tissues than in normal endometrium(P＜0.001)and correlated with lymph node metastasis and advanced FIGO stage(P＜0.05).BSP pro-tein level was also significantly elevated in HHUA cells(2.455 8±0.008 9)compared to HEECs(1.571 2±0.005 4)(P＜0.01).After knockdown,compared with the control group,the proliferation index(74.4±3.33),migration rate(0.48±0.03),and invasion ability(0.36±0.11)of the cells were increased,and the apoptosis rate(25.97％)of the cells was increased(P＜0.05).Furthermore,the expression levels of TGF-β signaling pathway downstream proteins TGF-β1(0.290 4±0.002 3)、TGF-β2(0.292 9±0.001 6)、Smad2(0.469 3±0.001 1)、Smad3(0.247 0±0.001 7)、pAKT(0.382 1±0.001 9)、ATK(0.119 6±0.001 6)and MEK1(0.258 9±0.000 3)in the BSP-knockdown group of EC cells decreased(P＜0.01).Conclusion BSP is highly expressed in endometrial cancer and promotes cancer cell proliferation,invasion,and metastasis by activating the TGF-β signaling pathway.

Copper is one of the essential elements in the human body,playing various physiological roles.Maintai-ning copper homeostasis is crucial for health.Recent researches have uncovered that copper homeostasis imbalance is closely associated with the occurrence,progression,prognosis,and drug resistance of gynecological malignancies.The employment of copper and its complexes in antitumor therapy has emerged as a promising novel approach,attracting considerable research attention.Based on the relationship between copper homeostasis imbalance and gynecological tumors,this paper provides a concise review of the current status and progress of copper and its complexes in the treat-ment of gynecological tumors.

Purpose To analyze and compare the impact of incorporating molecular classification into the new FI-GO(2023)staging system for endometrial cancer(EC).Methods A retrospective analysis was conducted on 332 ca-ses of EC diagnosed and molecular subtyped by Department of Pathology Tianjin Central Hospital of Gynecology Obstet-rics in 2023.All cases were staged according to the FIGO(2023)staging criteria for EC.Results The median age of the 332 EC patients was 56 years(range:27-76 years).Molecular subtypes included 30 POLE mutation(POLE-mut),80 mismatch repair deficiency(MMRd),194 no specific molecular profile(NSMP),and 28 p53 abnormal(p53abn).Significant differences were observed among the four molecular subtypes regarding age,FIGO stage,patho-logical type,and lymph node metastasis rate(P＜0.05).However,no significant differences were found in the depth of myometrial invasion or lymphovascular space invasion.In the POLEmut group,19 cases(63.33％)were of non-ag-gressive histological types and 11(36.67％)were aggressive.After incorporating molecular subtyping,all 11 stage Ⅱ patients were downgraded to stage Ⅰ AmPOLEmut,increasing the proportion of stage Ⅰ patients from 62.07％to 100％.In the p53abn group,9 cases(32.14％)were non-aggressive and 19(67.86％)were aggressive.Molecular integra-tion led to the upstaging of 4 stage Ⅰ patients with myometrial invasion to stage Ⅱ Cmp53abn,increasing the proportion of stage Ⅱ patients from 34.61％to 50％.Conclusion Molecular subtypes p53abn and POLEmut are associated with distinct alterations in EC staging,specifically leading to tumor upstaging or downstaging.Our findings underscore the critical importance of comprehensive molecular subtyping in EC staging,as it refines prognostic risk stratification and provides valuable guidance for adjuvant treatment decisions.

Purpose This study aims to explore the effect of peroxisomal membrane protein 4(PXMP4)on the migration and invasion of cervical cancer(CC)cells,as well as the epithelial-mesenchymal transition(EMT)process.Methods Bioinformatics and immunohistochemical analysis were employed to examine the expression of PXMP4 in CC tissues and its correlation with clinical pathological characteristics.Western blot and RT-qPCR were used to detect the expression of PXMP4 in CC cells.CCK-8 assay,scratch healing assay,and Transwell invasion assay were utilized to assess the proliferation,migration,and invasion capabilities of CC cells.Western blot was conducted to measure the expression of N-cadherin,E-cadherin,vimentin,phosphorylated ERK(p-ERK),and total ERK proteins in cervical CC.Results The TCGA database showed that the mRNA expression level of PXMP4 was significantly elevated in non-paired CC tissues(P=0.000 29),while the GEO database showed that the mRNA expression level of PXMP4 was sig-nificantly elevated in paired CC tissues(P=0.02).Immunohistochemical analysis showed that PXMP4 was primarily localized in the cytoplasm and cell membrane,with a positive rate of 70.31％(45/64)in CC tissues,significantly higher than 29.69％(19/64)in adjacent tissues.Clinical pathological analysis found that PXMP4 expression was as-sociated with maximum tumor differentiation(P=0.000 328)and lymph node metastasis(P=0.000 226),but not with age(P=0.637)or tumor diameter(P=0.304).CCK-8 assay,wound healing assay,and Transwell invasion as-say demonstrated that interference with PXMP4 inhibited the proliferation,invasion,and migration of CC cells,while overexpression of PXMP4 promoted these processes.Western blot results indicated that interference with PXMP4 signif-icantly increased E-cadherin expression and decreased N-cadherin,vimentin,and p-ERK expression(P＜0.05).Conversely,overexpression of PXMP4 led to a significant decrease in E-cadherin and an increase in N-cadherin,vim-entin,and p-ERK expression(P＜0.05).Additionally,stimulation of CC cells with different concentrations of the U0126 inhibitor significantly increased E-cadherin expression and decreased N-cadherin,vimentin,and p-ERK expres-sion(P＜0.05).Conclusion PXMP4 is highly expressed in CC tissues and is closely related to tumor differentiation and lymph node metastasis.PXMP4 promotes the EMT process of CC cells through the phosphorylated ERK1/2 signa-ling pathway.

The safety management of dangerous chemicals has been identified as a critical component in China's 14th Five-Year Plan for emergency response planning.In recent years,the regulatory framework and standards,as well as the supervisory system for dangerous chemicals,have been continuously improved,with the managing entities strengthening risk identification in key areas.Currently,regulations on dangerous chemicals primarily focus on produc-tion,transportation,and warehousing industries.However,for the medical sector,particularly pathological laboratories which account for a significant portion of total hospital usage,there are no industry standards or expert consensuses on the standardized management and safe use of dangerous chemicals.This article reviews the classification,safety man-agement system,storage requirements,waste disposal,emergency response,and fire protection measures for dangerous chemicals in pathological laboratories.Based on the latest national standards and regulations,combined with the condi-tions of hospitals and pathological laboratories,this article aims to develop an expert consensus on the safe use and standardized management of dangerous chemicals in pathological laboratories,providing actionable guidance for their standardized construction and safety management.

Purpose To investigate the role of tumor-associated neutrophils(TANs)in the sternness characteris-tics of breast cancer cells.Methods Flow cytometry was used to identify and validate the successful generation of TANs.Breast cancer cell lines were co-cultured with TANs-conditioned supernatant,and their sphere-forming capacity was assessed.Western blot and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)were used to detect the expression of stem cell-associated markers.In breast cancer clinical specimens,immunohistochemistry(IHC)was performed to quantify TANs infiltration and the expression of sternness-related markers.Correlations be-tween TANs infiltration and sternness marker expression,as well as their associations with clinicopathological features of breast cancer patients,were analyzed.Results Flow cytometry results demonstrated a significantly higher survival rate of TANs compared to normal neutrophils(NEUs)(P＜0.05).In vitro,TANs-derived supernatant significantly en-hanced the sphere-forming capacity of breast cancer cells compared to NEU-derived supernatant(P＜0.05).RT-qPCR analysis revealed that the mRNA expression levels of sternness-related markers such as CD133 and SOX9 in tumor cells was significantly increased after TANs supernatant co-cultured with breast cancer cells(P＜0.05).The results of western blot further confirmed that the protein expression levels of CD133 and SOX9 were markedly increased in the TANs supernatant group relative to the NEU supernatant group(P＜0.01).Immunophenotypic analysis showed that the infiltration density of CD66b+TANs in breast cancer tissues was positively correlated with the expression of CD133(r=0.429,P＜0.001)and SOX9(r=0.561,P＜0.001)in tumor cells.Prognostic and clinicopathological analy-ses indicated that patients in the high CD66b+TANs infiltration group,high CD133 expression group,and high SOX9 expression group had significantly shorter progression-free survival(PFS)than those in the corresponding low-expres-sion/infiltration groups(P＜0.05).Furthermore,the infiltration density of CD66b+TANs was significantly associated with patient age,histological grade,and lymph node metastasis status(all with P＜0.05).CD133 expression was cor-related with patient age,lymph node metastasis,and progesterone receptor(PR)status(all with P＜0.05),while SOX9 expression was associated with patient age and lymph node metastasis status(all with P＜0.05).Conclusion TANs can promote the acquisition and maintenance of sternness characteristics in breast cancer cells.These findings may provide novel insights into the development of neutrophil-targeted immunotherapeutic strategies for breast cancer.

Purpose This study aimed to evaluate the consistency of human epidermal growth factor receptor 2(HER2)status between primary breast cancer lesions and lung metastatic lesions and to establish a prognostic model for predicting the survival rate of HER2 low expression(HER2-low)breast cancer patients with lung metastasis.Methods Clinicopathological data from a cohort of 252 patients with breast cancer and lung metastasis were retrospec-tively analyzed.Results 50.00％of the patients had HER2-low expression in metastatic lesions,and HER2-low ex-pression was the most prevalent subgroup in both primary and metastatic lesions.A discordance in HER2 status be-tween primary and metastatic sites was observed in 28.07％of cases.The most frequent shift was from HER2-zero in the primary tumor to HER2-low expression in the metastasis(12.28％of all cases).Estrogen receptor(ER)status,menopausal status,and histological type were identified as independent prognostic factors for overall survival(OS)by univariate and multivariate Cox regression analyses.A prognostic model incorporating these factors was constructed to predict 3-year and 5-year survival.The model demonstrated area under the curve(AUC)values of 0.765 and 0.780 for 3-year and 5-year OS in the training cohort,and 0.667 and 0.706 in the validation cohort,respectively.Conclu-sion HER2-low expression is the most common subtype among breast cancer patients with lung metastasis.The ob-served shift from HER2-zero in primary lesions to HER2-low in metastases underscores the clinical necessity of re-biop-sy at metastatic sites.The developed prognostic model effectively predicts OS in this patient population.

Purpose To investigate the clinical significance of Gasdermin B(GSDMB)in ovarian cancer and its relationship with immune infiltration,aiming to explore novel biomarkers for immunotherapy.Methods Gene expres-sion matrix,somatic mutations,somatic copy number alterations(SCNA),and clinical data were obtained from the The Cancer Genome Atlas(TCGA)database.Copy number variation(CNV)analysis was performed using the GISTIC algorithm,and the CIBERSORT algorithm was applied to quantify the relative abundance of 22 immune cell types in the tumor microenvironment.Protein-protein interaction(PPI)network analysis was conducted to identify GSDMB-associ-ated interacting proteins.Additionally,multiplex immunofluorescence was used to verify the spatial distribution differ-ences of GSDMB protein in clinical ovarian cancer samples with different immune phenotypes and its interaction with immune cells.Results The expression level of the GSDMB gene was significantly higher in adjacent non-cancerous tissues than in tumor tissues(P＜0.001).Patients with high GSDMB expression exhibited elevated levels of immune chemokines(such as CXCL9 and CXCL10,P＜0.01)and tumor-killing lymphocytes(the proportion of CD8+T cell was significantly higher in the high-expression group than in the low-expression group,P＜0.001).CNV analysis re-vealed that GSDMB copy number alterations significantly influenced immune cell infiltration:patients with GSDMB cop-y number amplification had decreased infiltration levels of CD4+T cells and dendritic cells(P＜0.05),while those with deep deletion of GSDMB had significantly reduced infiltration levels of CD8+T cells and neutrophils(P＜0.01).PPI network analysis indicated that GSDMB might interact with key immune molecules,including IL-37,IL-18BP,IL-33,and IL-2(Pearson correlation coefficient r＞0.6,P＜0.001).Multiplex immunofluorescence analysis demonstra-ted that tumors with high GSDMB expression were more likely to exhibit an immune-inflamed phenotype(52.6％),while tumors in the low-expression group were predominantly immune-desert type(47.3％).Immunotherapy cohort a-nalysis suggested that GSDMB could serve as a potential predictive biomarker for immunotherapy responsiveness,with high predictive efficacy in multiple immune checkpoint inhibitor therapy cohorts targeting PD-1,PD-L1,and CTLA4(AUC＞0.8).Conclusion GSDMB plays a crucial role in reshaping the tumor microenvironment in ovarian cancer and may serve as a novel sensitizing target for immunotherapy.