China is a country with high incidence of digestive tract tumors.The three major digestive tract tumors,represented by gastric cancer,esophageal cancer,and colon cancer,seriously threaten the health of our people.This article reviewed the challenges faced in the pathological development of early gastrointestinal cancer,the changes in di-agnostic criteria for early gastrointestinal cancer,and the research progress on molecular subtyping of advanced gastro-intestinal cancer.In the diagnosis of early gastrointestinal cancer,pathologists should closely collaborate with clinical practice,improve the accuracy of early gastrointestinal cancer diagnosis through continuous learning and practice,make reasonable use of relevant molecular pathological methods to assist in guiding clinical treatment,and closely monitor the latest research progress of gastrointestinal tumors.

Purpose To investigate the clinicopathological features,immunophenotypic profile,differential diag-noses,and prognostic implications of liver metastatic solid pseudopapillary neoplasm(LMSPN).Methods A retro-spective analysis was conducted on the clinicopathological features,immunohistochemical profile,and clinical outcomes of of 15 cases of LMSPN cases,supplemented by a literature review.Results Of the 15 patients,12 were female and 3 were male,with a mean age of 43 years(range 25-67 years).Multiple hepatic lesions were observed in 9 cases,some of which were accompanied by abdominal or omental metastasis.The tumors exhibited a cystic-solid appearence on gross examination,ranging from 0.5 to 15 cm in diameter.Histologically,the tumors showed typical cystic-solid and pseudopapillary areas,with tumor cells arranged around small blood vessels forming characteristic pseudopapillary structures.Tumor cells exhibited relatively uniform morphology,however,some cases presented with tumor necrosis(5/15),cytologic/nuclear atypia(4/15),mitotic figures(5/15),lymphovascular invasion(6/15),perineural inva-sion(3/15),and lymph node metastasis(2/15).Immunohistochemically,tumor cells showed variable expression ofβ-catenin,LEF1,vimentin,CD10,α1-ACT,PR,E-cadherin,NSE,CD56,Syn and Ki67.Notably,the nuclear ex-pression level of Ki67 and PR were significantly associated with prognosis(P＜0.05).β-catenin,LEF1,PR,and Ki67 were predominantly expressed in the nuclei,while markers such as CKpan,CgA,Hep Par-1,Arginase-1,CK7,and CK19 were negative or only weakly expressed.Follow-up data were available for 11 patients(range 10-157 months).Four patients died of widespread hepatic and abdominal metastases,while 7 remained alive.Conclusion The liver is the most most frequent site of distant metastasis for solid pseudopapillary neoplasms of the pancreas.High expression of Ki67 and PR is associated with unfavorable prognosis in LMSPN.

Purpose To investigate the relationship between FN1 expression and clinical and pathologic features of laryngeal squamous cell carcinoma(LSCC)and the expression of tumor-associated macrophages(TAMs).Methods LSCC datasets GSE33232 and GSE84957 were analyzed and screened the differentially expressed gene FN1,and draw the receiver operating characteristic(ROC)curve.Bioinformatics analysis of FN1 expression,and prognosis in LSCC was performed.To investigate the effect of down-regulating FN1 expression in TU177 cells on the malignant bio-logical behavior of LSCC,we performed a scratch wound healing assay and a Transwell chamber assay to assess the effect of FN1 on cell proliferation,migration,and invasion in vitro.Immunohistochemical(IHC)staining was per-formed to detect the expression of FN1 and CD 163 in LSCC tissues.Results Analysis of the GSE33232 and GSE84957 datasets and online databases showed that FN1 was significantly overexpressed in LSCC tissues(P＜0.05),and patients with high FN1 expression had a significantly lower recurrence-free survival rate(HR=1.6,P=0.017).After transfection with si-FN1,the expression of FN1 in TU177 cells was significantly reduced(0.34±0.02 vs 1.00±0.03,P＜0.01).Compared with the control group,the down-regulation of FN1 expression inhibited the in vitro migra-tion(56.1±3.1 vs 19.23±1.0)and invasion(480±23 vs 288±20)ability of TU177 cells(both P＜0.01).Im-munohistochemistry findings showed that FN1 was highly expressed in both the tumor parenchyma(nest)and stromal cells of LSCC tissue,with a statistically significant difference[52.1％(24/46)vs 71.7％(33/46),P＜0.001].It was found that high expression of N-FN1 was associated with patients' pathological grade and lymph node metastasis(P＜0.05),while high expression of S-FN1 was associated with patients' age,lymph node metastasis,and TNM stage(P＜0.05).In addition,the co-expression of FN1 and CD163 was correlated with patients' pathological grad-ing,lymph node metastasis,and TNM stage(all P＜0.05).Conclusion FN1 and CD163 exhibit high expression levels in LSCC patients,which are closely associated with malignant progression,including invasion and metastasis.Notably,during LSCC progression,there may be a potential synergistic interaction between FN1 and CD 163-positive macrophages in the tumor microenvironment.

The histological assessment has been considered as a detailed and accurate method for measuring the disease activity in inflammatory bowel disease(IBD).In ulcerative colitis(UC),histological activity has been demon-strated to be associated with a higher rate of relapse,prolonged corticosteroid use and long-term complications,even in patients who have achieved endoscopic remission.Therefore,histological remission may be regarded as a potential ther-apeutic target.This article introduces the clinical significance of disease activity assessment in IBD,focusing on the re-view of validated and newly proposed histological scoring systems for IBD,and explores the priorities for future research needs.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.

Purpose To explore the expression of SHIP2 in esophageal squamous cell carcinoma and its effect on the malignant biological behavior of ESCC cells.Methods The UALCAN database was used to analyze the expression of SHIP2 in esophageal cancer.qRT-PCR and immunohistochemistry SP method were used to measure the expression of SHIP2 in tumor tissues of ESCC patients.SHIP2 mRNA and protein were examined by qRT-PCR and Western blot in human normal esophageal epithelial cells(HEEC)and ESCC cells(KYSE150 and EC109).KYSE150 and EC109 were divided into the NC group and the si-SHIP2 group respectively.Cell proliferation,migration,and invasion were observed by CCK-8 assay,EdU assay,scratch assay,and Transwell assay.The expression of epithelial-mesenchymal transition-related proteins(E-cadherin,N-cadherin,and vimentin)was detected by Western blot.Results The UAL-CAN database showed that SHIP2 expression was higher in esophageal cancer than in normal tissues(P＜0.05).SHIP2 had higher mRNA(2.19±3.20)expression and staining scores(5.33±3.83)in ESCC tumor tissues than in paracarcinoma tissues(1.00±0.80;0.87±1.07,all P＜0.05).SHIP2 had higher mRNA(KYSE150,EC109:1.91±0.22,3.73±1.06)and protein(KYSE150,EC109:0.93±0.12,1.05±0.13)expression in ESCC cells than in HEEC(1.06±0.40;0.31±0.04,all P＜0.05).Cell function experiments showed that compared with the NC group(CCK-8 assay:KYSE150,EC109:2.44±0.12,3.56±0.07;EdU assay:KYSE150,EC109:44.46±4.74,38.82±3.79;scratch assay:KYSE150,EC109:0.85±0.07,0.70±0.06;Transwell migration assay:KYSE150,EC109:130.30±9.53,39.25±3.30;Transwell invasion assay:KYSE150,EC109:121.00±9.54、88.67±6.66);cell proliferation(CCK-8 assay:KYSE150,EC109:1.56±0.03,2.85±0.02,EdU assay:KYSE150,EC109:19.34±6.24,17.39±1.14);migration(scratch assay:KYSE150,EC109:0.51±0.09,0.36±0.02;Transwell migration assay:KYSE150,EC109:71.50±12.07,20.75±2.99),and invasion(Transwell in-vasion assay:KYSE150,EC109:73.33±4.04,12.67±2.31)ability in the si-SHIP2 group was significantly re-duced(all P＜0.05).Western blot results showed that compared with the NC group(0.48±0.21,0.42±0.24;1.00±0.04,1.17±0.18;1.34±0.10,1.00±0.13),the expression of E-cadherin protein(1.10±0.22,1.02±0.20)in the si-SHIP2 group was increased(P＜0.05),while the expression of N-cadherin protein(0.59±0.20,0.84±0.08)and vimentin protein(0.41±0.06,0.338±0.19)was decreased(P＜0.05).Conclusion SHIP2 is overexpressed in ESCC,and the down-regulation of SHIP2 can inhibit the proliferation,migration,and invasion of ES-CC cells.

Purpose To investigate the expression of POLR2M in colorectal cancer(CRC)and its effects on cell growth,apoptosis and invasion.Methods GEPIA2.0,TCGA and Kaplan-Meier Plotter databases were used to ana-lyze the differential expression of POLR2M in CRC tissues and normal adjacent tissues,and to evaluate its prognostic significance using the Log-rank test.Quantitative real-time PCR(qRT-PCR)was used to detect the expression of POLR2M in human colorectal cancer cell lines SW480,HCT-8,RKO,LOVO,DLD-1,HCT-116,SW620 and human normal colorectal cell line FHC.DLD-1 and RKO cells were stably transfected with lentivirus,and the POLR2M groups were up-regulated into the control group(LV-NC)and experimental group(LV-POLR2M),and the transient transfec-tion of SW620 and SW480 cells with interfering fragments of SiRNA was used to down-regulate the POLR2M groups into the control group(Si-NC)and experimental group(Si-POLR2M),and the transfection efficiency of each group was verified.CCK-8,plate cloning,Transwell and scratch healing assays were used to detect cell proliferation,invasion and migration.Flow cytometry was used to detect the effects of POLR2M on cell cycle and apoptosis.Results GE-PIA2.0,TCGA and Kaplan-Meier Plotter database analysis showed that the expression of POLR2M in colorectal cancer was significantly higher than in normal adjacent tissues(P＜0.05),and the expression of POLR2M was closely associ-ated with the histological type of colorectal cancer and lymph node metastasis(P＜0.05),but not with the age,gen-der,tumor grade and vascular invasion of patients(P＞0.05).The prognosis of patients with POLR2M overexpression was poor(P＜0.05).The results of qRT-PCR showed that compared with FHC cells,the mRNA expression of POLR2M in SW480,HCT-8,RKO,LOVO,DLD-1,HCT-116 and SW620 cell lines was increased(F=97.7,P＜0.05),and POLR2M stable overexpression and interference cell lines were successfully constructed.Compared with the LV-NC group,the viability,colony number,number of cells passing through the chamber and cell mobility of DLD-1 and RKO cells in the LV-POLR2M group were significantly increased(P＜0.05).Compared with the Si-NC group,the viability,colony number,number of cells passing through the chamber,and cell mobility of SW620 and SW480 cells in the Si-POLR2M group were significantly decreased(P＜0.05).Downregulation of POLR2M induced cell cycle arrest in G1 phase and promotes apoptosis(P＜0.05).Conclusion POLR2M may play a role as a pro-tumor gene in CRC,and its high expression can significantly promote the proliferation and invasion of CRC cells.

Purpose To investigate correlation of ADP ribosylation-like factor 6 interacting protein 4(ARL6IP4)expression with the pathological characteristics and clinical prognosis in primary colon cancer.Methods The ARL6IP4 mRNA expression in tumor and adjacent normal tissues of 133 colon cancer patients was analyzed by RT-qPCR,and its relationship with tumor location,pathological TNM stage,and 3-year survival prognosis was assessed.Additionally,ARL6IP4 protein expression was analyzed by immunohistochemistry in 30 cases,of which 16 cases were analyzed by immunofluorescence.Results The colon cancer presented significantly higher mRNA and protein levels of ARL6IP4 than adjacent normal tissues(t=4.221,P=5.200 × 10-5;t=7.421,P=3.537 × 10-8).The relative ex-pression level of ARL6IP4 mRNA in colon cancer was positively correlated with pathological TNM stage,N stage and M stage(P＜0.05),and negatively correlated with 3-year cumulative survival probability(P＜0.01).Additionally,sig-moid colon cancer presented significantly higher ARL6IP4 expression than other colon cancers,and at the cellular lev-el,ARL6IP4 was predominantly expressed in the cell nucleus.Conclusion The ARL6IP4 expression in colon cancer is higher than that in adjacent normal tissues,which is closely related to tumor metastasis and clinical prognosis.

Purpose To investigate the clinicopathological significance of peritumoral retraction clefts(PRC)in esophageal squamous cell cancer(ESCC)and its correlation with prognosis.Methods 266 cases of esophageal squa-mous cell carcinoma were collected.Excluding the cases due to incomplete clinical data,cracks caused by the produc-tion process,and receiving preoperative adjuvant treatment,248 cases were finally counted.PRC was determined by the proportion of retraction clefts in the tumor volume of 10％.A retrospective analysis was conducted to explore the re-lationship between PRC and the clinicopathological features as well as prognosis of ESCC.Results Among 248 ESCC patients,114 cases had PRC,while 134 cases did not.Correlation analysis showed that PRC was closely related to his-tological grade,lymphatic invasion,lymph node metastasis,depth of tumor invasion and TNM stage of ESCC,and ES-CC patients with PRC were more likely to have lymphatic invasion and lymph node metastasis(P＜0.05).In patients without lymphatic invasion,the probability of nodal metastasis in patients with PRC was higher than those without PRC,and the difference was statistically significant(P＜0.001).Kaplan-Meier survival analysis showed that 5-year overall survival(P=0.001)and progression-free survival(P=0.002)in ESCC patients with PRC were significantly lower than those without PRC.Conclusion ESCC patients with PRC are more likely to have local invasiveness,lymphatic invasion and nodal metastasis,may predict the poor prognosis of ESCC patients.Patients with nodal metastasis are more common with PRC.

Purpose To characterize the clinicopathological features of gastrointestinal mesenchymal tumors(GMTs)resected via endoscopic techniques.Methods A retrospective analysis was conducted on 495 cases of endo-scopically resected GMTs.Clinical information,histomorphological findings,immunohistochemical profiles,and mo-lecular characteristics were reviewed.Results The cohort included 495 patients aged 20-78 years(median:53 years).The majority of tumors were located in the stomach(58.8％)and esophagus(36.8％).Histologically,most tumors consisted of spindle cells,with a minority composed of epithelioid cells;fibrocollagenous or myxoid stroma was occasionally observed.Immunohistochemically,leiomyomas showed diffuse positivity for α-SMA(98.8％)and desmin(99.3％),gastrointestinal stromal tumors(GISTs)expressed CD117(99.4％),DOG1(97.6％),and CD34(97.0％),and schwannomas were positive for S-100(93.7％).The predominant tumor types were leiomyomas(54.1％)and GISTs(33.7％),while the remaining 12.2％comprised other rare types.Various endoscopic resection techniques were employed based on the tumors' anatomical depth,including endoscopic submucosal dissection(ESD,40.5％),submucosal tunneling endoscopic resection(STER,17.1％),endoscopic mucosal resection(EMR,16.5％),endoscopic full-thickness resection(EFTR,13.9％),and endoscopic submucosal excavation(ESE,12.0％).EMR and ESD were primarily used for superficial lesions,while deeper tumors with were more often treated with STER,EFTR,and ESE.The rate of negative resection margins was lower in GISTs(72.2％)and other tumors with indistinct margins,compared to leiomyomas(92.6％)and those with well-defined boundaries.Conclusion Leiomyomas and GISTs are the most common gastrointestinal mesenchymal tumors resected via endoscopy.A variety of resection techniques are applicable depending on tumor location and depth.Accurate pathological diagnosis should be based on HE morphology,supplemented by endoscopic findings,margin status,immunohistochemistry,and necessary molecular tests.