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Comparison of mismatch repair and immune checkpoint protein profile with histopathological parameters in pancreatic,periampullary/ampullary,and choledochal adenocarcinomas

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 875-882页

作者： Arzu Hazal Aydın Nesrin Turhan Department of pathology Aksaray University Aksaray Training and Research HospitalAksaray 68200Turkey Department of pathology University of Health Sciences Ankara City HospitalAnkara 06800Turkey

BACKGROUND Pancreatic,periampullary/ampullary,and choledochal adenocarcinomas are aggressive malignancies with a poor prognosis.Immune checkpoint blockade is a promising treatment option for several tumor types.H long terminal repeatassociating 2(HHLA2),which is analogous to programmed death-ligand 1(PDL1),is a recently discovered member of the B7/cluster of differentiation 28 family and is expressed in many malignancies.AIM To analyze the expression of HHLA2 and its association with the pathologic biomarkers that predict sensitivity to immunotherapy.METHODS Ninety-two adenocarcinoma cases located in the pancreas,ampulla,and distal common bile duct were identified.This study assessed 106 pancreaticoduodenectomy and distal/total pancreatectomy samples that were delivered to Ankara City Hospital between 2019 and 2021.Immunohistochemistry was conducted to examine the expression of DNA mismatch repair(MMR),PD-L1,and HHLA2 proteins.RESULTS Patients with high HHLA2 expression had a higher mean age than those with low expression.Low HHLA2 expression was associated with high perineural invasion.HHLA2 expression was low in pathological stage T3(pT)3 cases and high in pathological stage T1,T2,and T4 cases.There was no correlation between HHLA2 expression and the expression of MMR proteins and PD-L1.CONCLUSION Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy and may serve as a novel therapeutic target for immunotherapy in advanced-stage disease.

关键词： H long terminal repeat-associating 2 Programmed death-ligand 1 Adenocarcinoma Pancreas Ampulla of Vater Distal common bile duct

Liver biopsy in the post-hepatitis C virus era in Japan

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World Journal of Gastroenterology 2024年第14期30卷 1949-1957页

作者： Yoshihiro Ikura Takako Okubo Yasuhiro Sakai Department of pathology Takatsuki General HospitalTakatsuki 569-1192Osaka PrefectureJapan Department of pathology Kansai Medical University Medical CenterMoriguchi 570-8507Japan

In Japan,liver biopsies were previously crucial in evaluating the severity of hepatitis caused by the hepatitis C virus(HCV)and diagnosing HCV-related hepatocellular carcinoma(HCC).However,due to the development of effective antiviral treatments and advanced imaging,the necessity for biopsies has significantly decreased.This change has resulted in fewer chances for diagnosing liver disease,causing many general pathologists to feel less confident in making liver biopsy diagnoses.This article provides a comprehensive overview of the challenges and potential solutions related to liver biopsies in Japan.First,it highlights the importance of considering steatotic liver diseases as independent conditions that can coexist with other liver diseases due to their increasing prevalence.Second,it emphasizes the need to avoid hasty assumptions of HCC in nodular lesions,because clinically diagnosable HCCs are not targets for biopsy.Third,the importance of diagnosing hepatic immune-related adverse events caused by immune checkpoint inhibitors is increasing due to the anticipated widespread use of these drugs.In conclusion,pathologists should be attuned to the changing landscape of liver diseases and approach liver biopsies with care and attention to detail.

关键词： Liver biopsy Alteration Post-hepatitis C virus era Steatotic liver disease Hepatic tumors Immune checkpoint inhibitors

Blastomas of the digestive system in adults:A review

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1030-1042页

作者： Yu Liu Tony El Jabbour Jonathan Somma Yukihiro Nakanishi Saverio Ligato Hwajeong Lee Zhi-Yan Fu Department of pathology LSU Health Sciences Center School of MedicineNew OrleansLA 70112United States Department of pathology Hartford HealthCareHartfordCT 06102United States Department of pathology Moffitt Cancer CenterTampaFL 33612United States Department of pathology and Laboratory Medicine Albany Medical CenterAlbanyNY 12208United States

Blastomas,characterized by a mixture of mesenchymal,epithelial,and undifferentiated blastematous components,are rare malignant neoplasms originating from precursor blast cells.This review focuses on digestive system blastomas in adult patients,including gastroblastoma,hepatoblastoma,and pancreatoblastoma.Gastroblastoma is a biphasic,epitheliomesenchymal tumor,with only sixteen cases reported to date.In addition to the characteristic histology,metastasisassociated lung adenocarcinoma transcript 1-glioma-associated oncogene homolog 1 gene fusion is typical,although recently novel ewing sarcoma breakpoint region 1-c-terminal binding protein 1 and patched 1-glioma-associated oncogene homolog 2 fusions have been described.Hepatoblastoma is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic difficulty.Pancreatoblastoma,primarily a pediatric tumor,displays acinar differentiation and squamoid nests with other lines of differentiation also present,especially neuroendocrine.Diagnostic approaches for these blastomas include a combination of imaging modalities,histopathological examination,and molecular profiling.The treatment generally involves surgical resection,which may be supplemented by chemotherapy or radiotherapy in some cases.Prognoses vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes,particularly in the setting of metastases.This review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.

关键词： Adult blastomas Gastroblastoma Hepatoblastoma Pancreatoblastoma Digestive system

Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1878-1889页

作者： Fouzia Fazal Muhammad Arsalan Khan Sumayya Shawana Rahma Rashid Muhammed Mubarak Department of pathology Jinnah Medical and Dental CollegeKarachi 74800SindhPakistan Department of General Surgery Sindh Institute of Urology&Transplantation(SIUT)Karachi 74200SindhPakistan Department of pathology Bahria University of Health SciencesKarachi 74400SindhPakistan Department of pathology SIUTKarachi 74200SindhPakistan

BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 subset.AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors.METHODS A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC patients.Using CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 proportion.Demographic,histopathological,and clinical parameters were collected.RESULTS TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both zones.The tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors.CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples.We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and LVI.This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.

关键词： Colorectal cancer Macrophages Tumor stroma M2 subset Tumor front Tumor stage Lymphovascular invasion Prognosis Tumor-associated macrophages Immunohistochemistry

Microbiome changes in esophageal cancer:implications for pathogenesis and prognosis

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Cancer Biology & Medicine 2024年第2期21卷 163-174页

作者： Yi Li Bing Wei Xia Xue Hongle Li Jun Li Department of Molecular pathology Clinical Pathology CenterAffiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhou 450003China Henan Key Laboratory of Molecular pathology Zhengzhou 450003China Henan Key Laboratory of Helicobacter pylori&Microbiota and Gastrointestinal Cancer Marshall Medical Research CenterThe Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Esophageal cancer(EC)is an aggressive malignancy with a poor prognosis.Various factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal microbiome.Conversely,enrichment and diversity of the esophageal microbiome can also impact its function.Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC,thus suggesting the potential contribution of the esophageal microbiome to EC development.Additionally,distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy,indicating the role of the esophageal microbiome in modulating treatment outcomes.In this review,we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases,with a focus on identifying microbial communities associated with EC pathogenesis and prognosis.Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies,ultimately leading to better outcomes for patients.

关键词： Esophageal cancer microbiome dysbiosis microenvironment carcinogenesis

Single nucleotide polymorphism within chromosome 8q24 is associated with prostate cancer development in Saudi Arabia

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Asian Journal of Urology 2024年第1期11卷 26-32页

作者： Awad Elsid Osman Sahar Alharbi Atif Ali Ahmed Asim Ali Elbagir pathology and Clinical Laboratory Management Department(PCLM) King Fahad Medical CityRiyadhSaudi Arabia Department of pathology and Laboratory Medicine University of Missouri at Children's Mercy HospitalKansas CityMOUSA

Objective: Genome-wide association studies have demonstrated that single nucleotide polymorphisms (SNPs) are important risk factors for the development of prostate cancer (PCa). Preliminary studies have suggested that the incidence of PCa in Saudi males is low but is probably familial or genetically related.Methods: To identify any possible association of SNP with PCa development in Saudi patients, we investigated a group of SNPs in Saudi PCa patients (n=85) and compared the outcomes to healthy normal controls (n=115) and nodular hyperplasia patients (n=120). DNA was extracted from paraffin-embedded formalin fixed tissue or whole blood from both patients’ groups and healthy control group. A total of thirteen SNPs were genotyped using TaqMan® minor groove binder polymerase chain reaction assay.Results: The rs16901979A, s629242T and rs1447295A alleles were found at significantly higher frequency in PCa patients than controls (p< 0.05). The rs16901979 CA genotype was found at significantly greater frequency in PCa patients than in healthy controls (43% vs. 14%, odds ratio=4.6, p=0.0001) and benign hyperplasia group (43% vs. 25%, odds ratio=2.2, p=0.009).Conclusion: Our study has highlighted the association of rs16901979 SNP with PCa in Saudi males. Such findings have important implications in the PCa diagnosis and in screening unaffected family members of Saudi patients.

关键词： Prostatecancer Saudi Singlenucleotide polymorphism Allele

Role of ACLY in the development of gastric cancer under hyperglycemic conditions

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Quantitative Biology 2024年第1期12卷 100-116页

作者： Keran Sun Jingyuan Ning Keqi Jia Xiaoqing Fan Hongru Li Jize Ma Meiqi Meng Cuiqing Ma Lin Wei Department of Immunology Immunology Department of Hebei Medical UniversityShijiazhuangChina Department of pathology Pathology Department of the Fourth Hospital of Hebei Medical UniversityShijiazhuangChina

To investigate the impact of hyperglycemia on the prognosis of patients with gastric cancer and identify key molecules associated with high glucose levels in gastric cancer development,RNA sequencing data and clinical features of gastric cancer patients were obtained from The Cancer Genome Atlas(TCGA)database.High glucose-related genes strongly associated with gastric cancer were identified using weighted gene co-expression network and differential analyses.A gastric cancer prognosis signature was constructed based on these genes and patients were categorized into high-and low-risk groups.The immune statuses of the two patient groups were compared.ATP citrate lyase(ACLY),a gene significantly related to the prognosis,was found to be upregulated upon high-glucose stimulation.Immunohistochemistry and molecular analyses confirmed high ACLY expression in gastric cancer tissues and cells.Gene Set Enrichment Analysis(GSEA)revealed the involvement of ACLY in cell cycle and DNA replication processes.Inhibition of ACLY affected the proliferation and migration of gastric cancer cells induced by high glucose levels.These findings suggest that ACLY,as a high glucose-related gene,plays a critical role in gastric cancer progression.

关键词： ACLY gastric cancer high glucose immune microenvironment

Unveiling a new regulator: Vacuolar V-ATPase mediates brassinosteroid signaling in Arabidopsis

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Molecular Plant 2024年第2期17卷 227-229页

作者： Shikha Malik Justin W.Walley Department of Plant pathology Entomologyand Microbiologylowa State UniversityAmesIA 50011USA

Plant growth and development are intricately regulated by hormones such as auxins,gibberellins,jamonates,cytokinins,and brassinosteroids(BRs).BRs are a group of plant steroid hormones that play a vital role in plant growth and response to the environment.BRs regulate many biological processes including cell elongation,cell division,and male fertility,as well as abiotic and biotic stress responses.

关键词： media fertility brassinosteroid

Liquid biopsy for gastric cancer:Techniques,applications,and future directions

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World Journal of Gastroenterology 2024年第12期30卷 1680-1705页

作者： Cristina Díaz del Arco M Jesús Fernández Aceñero Luis Ortega Medina Department of Surgical pathology Health Research Institute of the Hospital Clínico San CarlosHospital Clínico San CarlosMadrid 28040Spain Department of Legal Medicine Psychiatry and PathologyUniversidad Complutense de MadridMadrid 28040Spain

After the study of circulating tumor cells in blood through liquid biopsy(LB),this technique has evolved to encompass the analysis of multiple materials originating from the tumor,such as nucleic acids,extracellular vesicles,tumor-educated platelets,and other metabolites.Additionally,research has extended to include the examination of samples other than blood or plasma,such as saliva,gastric juice,urine,or stool.LB techniques are diverse,intricate,and variable.They must be highly sensitive,and pre-analytical,patient,and tumor-related factors significantly influence the detection threshold,diagnostic method selection,and potential results.Consequently,the implementation of LB in clinical practice still faces several challenges.The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases,monitoring treatment response,early identification of relapses,or assessing patient risk.On the other hand,gastric cancer(GC)is a disease often diagnosed at advanced stages.Despite recent advances in molecular understanding,the currently available treatment options have not substantially improved the prognosis for many of these patients.The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients.In this comprehensive review,from a pathologist’s perspective,we provide an overview of the main options available in LB,delve into the fundamental principles of the most studied techniques,explore the potential utility of LB application in the context of GC,and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.

关键词： Liquid biopsy Gastric cancer Circulating tumor cells Cell-free DNA Circulating tumor DNA Molecular