Pathology, research and practice最新文献

{"title":"Targeting FOXM1/PSAT1 axis by Brusatol inhibits lung cancer malignant progression","authors":"Siyi Ou ,&nbsp;Xiaobo Wang ,&nbsp;Yulan Sun ,&nbsp;Yongfeng Liang ,&nbsp;Jing Bai ,&nbsp;Chuanchun Han ,&nbsp;Jing Song","doi":"10.1016/j.prp.2026.156365","DOIUrl":"10.1016/j.prp.2026.156365","url":null,"abstract":"<div><div>Brusatol (BRU), an extract from Brucea javanica, has been found to inhibit cancer progression. However, the downstream targets of Brusatol and its underlying mechanisms in lung cancer still not fully elucidate and warrant further investigation. Here, we identified that Brusatol significantly downregulated the mRNA and protein levels of phosphoserine aminotransferase 1 (PSAT1). Notably, overexpression of PAST1 could impair the antitumour effects of Brusatol on lung cancer cells in vitro and in vivo. Further mechanism studies revealed that FOXM1, an important transcription factor, was directly bound to the promoter of PSAT1, facilitating its transcription. Besides, FOXM1 upregulation antagonizes Brusatol’s suppression of PSAT1 and sustains tumor cell viability. Collectively, our data suggested that the FOXM1/PSAT1 axis might play an important role in the antitumour effects of Brusatol and that Brusatol may hold promise as a novel therapeutic strategy for lung cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156365"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactylation of HK2 facilitates cisplatin resistance in NSCLC by promoting cell migration, invasion, and glycolysis","authors":"Fanrui Zeng ,&nbsp;Wenyang Wang ,&nbsp;Peng Liu ,&nbsp;Qingsi Zeng","doi":"10.1016/j.prp.2025.156349","DOIUrl":"10.1016/j.prp.2025.156349","url":null,"abstract":"<div><h3>Objective</h3><div>Cisplatin (DDP) resistance has markedly diminished the efficacy of DDP-based chemotherapy in non-small cell lung cancer (NSCLC). Glycolysis represents a key contributor to NSCLC progression. Lactylation, a novel epigenetic modification, directly regulates glycolysis-associated gene expression. This study aimed to investigate whether lactylation-mediated modulation of glycolytic genes contributes to DDP resistance in NSCLC.</div></div><div><h3>Methods</h3><div>Cell viability, migration, and invasion capacities in parental and resistant NSCLC cells were assessed using cell counting kit-8 and Transwell migration/invasion assays. RT-qPCR and Western blot analyses were employed to quantify mRNA and protein levels of glycolytic markers. A xenografted tumor model was established to evaluate in vivo tumor progression.</div></div><div><h3>Results</h3><div>DDP-resistant NSCLC cells exhibited elevated glycolysis activity and increased lactylation levels of hexokinase 2 (HK2). Moreover, HK2 lysine lactylation (Kla) and protein stability were enhanced in resistant cells through suppression of ubiquitination. Functional experiments demonstrated that HK2 downregulation inhibited cell viability, migration, invasion, and glycolytic metabolism in A549/DDP and H1229/DDP cells, with these effects being reversed following sodium lactate treatment. Crucially, the glycolytic inhibitor 2-deoxy-<span>D</span>-glucose (2-DG) abrogated this rescue, and a K873R lactylation-deficient mutant failed to restore the malignant phenotype, confirming the specificity of the mechanism. <em>In vivo</em> studies further confirmed that HK2 inhibition suppressed tumor growth.</div></div><div><h3>Conclusions</h3><div>Lactylation at K873 stabilized HK2 by inhibiting its ubiquitination, which in turn drove glycolytic flux and promoted malignant behaviors in DDP-resistant NSCLC. This HK2 lactylation-stabilization axis represents a novel mechanism underlying chemoresistance and a promising therapeutic target for overcoming DDP resistance in NSCLC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156349"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145904013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of CCL22 and its histamine-associated modulation in the tumor microenvironment of tongue squamous cell carcinoma","authors":"Satoshi Kimura ,&nbsp;Shohei Shimajiri ,&nbsp;Ayumi Nitta ,&nbsp;Hiroaki Sato ,&nbsp;Hirotsugu Noguchi ,&nbsp;Toshiyuki Nakayama","doi":"10.1016/j.prp.2026.156373","DOIUrl":"10.1016/j.prp.2026.156373","url":null,"abstract":"<div><div>Tongue squamous cell carcinoma (SCC), the most common type of oral cancer, remains a major clinical challenge due to its aggressive behavior and poor prognosis in advanced stages. Standard treatments, including surgery, radiation therapy, and chemotherapy, provide limited benefit highlighting the need for novel therapeutic strategies. Recently, immunotherapy has emerged as a promising approach, largely through its ability to reshape the tumor microenvironment (TME). Increasing evidence indicates that chemokine signaling plays a critical role in tongue SCC by orchestrating the recruitment and function of immune regulatory cells. In particular, CC chemokine ligand 22 (CCL22), mainly produced by tumor-associated macrophages and dendritic cells, promotes the accumulation of CC chemokine receptor 4 (CCR4)–expressing regulatory T cells, consequently establishing an immunosuppressive TME and facilitating tumor progression and immune evasion. Furthermore, emerging studies suggest that histamine-related pathways within the TME can induce CCL22 expression, subsequently amplifying immunosuppressive feedback loops and further modulate tumor–immune interactions, although their precise roles in tongue SCC remain incompletely understood. A deeper understanding of these intertwined networks may uncover new therapeutic targets and enhance the efficacy of existing immunotherapies, including immune checkpoint inhibitors. This review provides an updated overview of the immune landscape of tongue SCC, with special emphasis on the CCL22–CCR4 axis and its interaction with histamine signaling. A deeper understanding of CCL22- and histamine-mediated pathways may contribute to the development of more effective and personalized immunotherapy strategies for tongue SCC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156373"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic reticulum stress and the unfolded protein response in ischemic nephropathy: Pathogenic mechanisms and emerging therapeutic strategies","authors":"Janavie Patel,&nbsp;Siddhi Bagwe Parab,&nbsp;Gaurav M. Doshi","doi":"10.1016/j.prp.2026.156367","DOIUrl":"10.1016/j.prp.2026.156367","url":null,"abstract":"<div><div>One of the main causes of chronic kidney disease (CKD), ischemic nephropathy, is brought on by maladaptive cellular stress responses, specifically endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signalling, in addition to vascular insufficiency. The primary goals of UPR activation via the Protein kinase R-like ER kinase (PERK), Inositol-requiring enzyme 1 (IRE1), and Activating Transcription Factor 6 (ATF6) pathways are to support renal tubular cell survival and restore proteostasis. Prolonged or severe ER stress, on the other hand, causes the UPR to shift toward pathogenic outcomes by triggering apoptotic (C/EBP homologous protein [CHOP], caspase-12), inflammatory (c-Jun N-terminal Kinase [JNK], nuclear factor kappa B [NF-κB]), and fibrotic (transforming growth factor-beta [TGF-β]/SMAD) cascades that lead to progressive renal dysfunction, tubular atrophy, and interstitial fibrosis. Furthermore, ER-mitochondria crosstalk connects acute ischemia injury to chronic fibrosis by exacerbating mitochondrial failure, oxidative stress, and cell death. Targeting therapy requires an understanding of the UPR's dual nature, which is beneficial during brief stress but harmful during prolonged ischemia. Promising approaches to maintain kidney function include interventions that alter particular UPR branches, improve autophagy, lower oxidative damage, and restore ER equilibrium. In addition to outlining the molecular bases of ER stress and UPR in ischemic nephropathy, this review suggests innovative therapeutic strategies meant to shift the equilibrium from maladaptive to adaptive stress responses, providing novel possibilities to slow or alter the course of CKD. This review aims to critically evaluate the molecular mechanisms of ER stress and the UPR in ischemic nephropathy, with a focus on identifying potential therapeutic strategies to preserve renal function and slow CKD progression.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156367"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNF6 activates JNK/c-JUN pathway in ovarian cancer by promoting K48-linked NME4 ubiquitination","authors":"Taoqiong Li,&nbsp;Fei Qian,&nbsp;Yumei Chen,&nbsp;Wei Li","doi":"10.1016/j.prp.2026.156366","DOIUrl":"10.1016/j.prp.2026.156366","url":null,"abstract":"<div><h3>Background</h3><div>RING finger protein 6 (RNF6), a member of the E3 ubiquitin ligase family, has been implicated in various cancers, yet its functional significance and regulatory mechanisms in ovarian cancer (OC) are poorly understood.</div></div><div><h3>Methods</h3><div>RNF6 expression levels were analyzed using TCGA data and confirmed by IHC, qRT-PCR, and western blotting in OC tissues or cell lines. Functional roles of RNF6 were evaluated through CCK-8, colony formation, wound healing, Transwell, and EMT marker assays. Protein interactions and ubiquitination patterns were investigated via Co-IP, CHX chase, and ubiquitination assays. Rescue experiments were conducted by co-modulating RNF6 and NME4 expression. In vivo tumorigenesis was assessed using a nude mouse xenograft model.</div></div><div><h3>Results</h3><div>RNF6 was markedly overexpressed in OC and associated with poor prognosis. Silencing RNF6 suppressed cell growth, invasive behavior, and EMT, while enhancing NME4 expression. Mechanistic analyses demonstrated that RNF6 directly binds to NME4 and facilitates its K48-linked polyubiquitination, leading to proteasomal degradation. Knockdown of NME4 reversed the tumor-suppressive effects of RNF6 depletion and reinstated JNK/c-JUN pathway activation. In vivo, RNF6 silencing significantly reduced tumor burden and impaired downstream signaling events.</div></div><div><h3>Conclusion</h3><div>RNF6 contributed to OC malignancy by destabilizing NME4 and activating the JNK cascade. This newly identified RNF6/NME4/JNK axis provides potential targets for therapeutic intervention in OC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156366"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the master of the replication fork—PCNA","authors":"Yuanhang Gong ,&nbsp;Weilan Hu ,&nbsp;Min Li","doi":"10.1016/j.prp.2026.156370","DOIUrl":"10.1016/j.prp.2026.156370","url":null,"abstract":"<div><div>Proliferating cell nuclear antigen (PCNA) orchestrates DNA replication, repair, stress responses, and cell-cycle control. Because tumors are hyperproliferative and genomically unstable, they are highly dependent on PCNA, creating a therapeutic vulnerability. Strategies under evaluation include direct inhibition of PCNA, disruption of PCNA–partner interactions that govern DNA metabolism and cell-cycle progression, and combination regimens with DNA-damaging agents to enhance chemo- and radiosensitivity. Several agents—most notably the APIM peptide ATX-101 and the allosteric small molecule AOH1996—have progressed beyond preclinical testing and are being evaluated as monotherapies or in combination with radiotherapy and genotoxic chemotherapies in early clinical studies. This review synthesizes the mechanistic rationale, therapeutic modalities, and development landscape of PCNA-targeted interventions, highlighting their potential to improve anticancer efficacy while mitigating toxicity.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156370"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNF125 suppresses stem cell-like properties and metastasis in non-small cell lung cancer by promoting ubiquitination and degradation of DDX5","authors":"Xuechun Leng ,&nbsp;Zhongwu Hu ,&nbsp;Mingzhi Zhang ,&nbsp;Qiuni Chen ,&nbsp;Keping Xu ,&nbsp;Jun Zhao","doi":"10.1016/j.prp.2026.156378","DOIUrl":"10.1016/j.prp.2026.156378","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) is the most frequent subclass of lung cancer with a gloomy prognosis. Ring finger protein 125 (RNF125), as a ubiquitin E3 ligase, functions on the progression and development of various tumors. This study attempted to address the function and mechanism of RNF125 in NSCLC. The level of RNF125 was predicted with GEPIA2 website and verified in tumor tissues from NSCLC patients. The role of RNF125 in the malignant processes of NSCLC was determined by cell counting kit-8, the 5-ethynyl-2′-deoxyuridine (EdU) incorporation, transwell, flow cytometry and sphere‑formation experiments. The ubiquitinated role of RNF125 on DEAD-box helicase 5 (DDX5) was assessed by co-immunoprecipitation, ubiquitination and cycloheximide assays. The function of RNF125 was revealed in xenografted mice. Low RNF125 expression predicted poor prognosis in NSCLC. RNF125 inhibited the levels of indexes involved in proliferation, migration, invasion and stemness, but promoted apoptosis rate in both A549 and H1299 cells. Mechanically, RNF125 directly bound to DDX5. Overexpression of RNF125 enhanced the DDX5 ubiquitination, but knockdown of RNF125 reduced the degradation of endogenous DDX5. The inhibitory role of RNF125 overexpression in the malignant progressions of A549 cells was recovered with the upregulation of DDX5, <em>vice versa</em>. Besides, overexpression of RNF125 declined tumor weight and volume, the level of Ki-67 and the numbers of liver metastasis foci <em>in vivo</em>, <em>vice versa</em>. Also, RNF125 overexpression reduced the protein expressions of invasion markers and stemness markers <em>in vivo</em>. Collectively, low expression of RNF125 predicted poor prognosis of NSCLC patients. Upregulation of RNF125 repressed proliferation, mobility, invasion and stemness of NSCLC through the ubiquitinated degradation of DDX5.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156378"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of exosomes in malignancies: From drug delivery to clinical application","authors":"Roshni Bibi,&nbsp;Arunika Koley,&nbsp;Koustav Sarkar","doi":"10.1016/j.prp.2026.156381","DOIUrl":"10.1016/j.prp.2026.156381","url":null,"abstract":"<div><h3>Background</h3><div>Cancer remains one of the most pressing global health challenges, with conventional treatments such as chemotherapy and radiotherapy constrained by modest efficacy and severe long‑term adverse effects. Exosomes—nano‑sized extracellular vesicles (30–150 nm) secreted by diverse cell types—have emerged as promising candidates for cancer diagnosis and therapy due to their inherent biocompatibility, low immunogenicity, and ability to cross biological barriers.</div></div><div><h3>Methods</h3><div>A comprehensive review of recent literature was conducted to summarize advancements in exosome biology, isolation techniques, and engineering strategies relevant to cancer nanomedicine. Particular emphasis was placed on ESCRT (Endosomal Sorting Complex Required for Transport) dependent biogenesis mechanisms, molecular cargo profiling, and applications in targeted drug delivery.</div></div><div><h3>Results</h3><div>Tumor‑derived exosomes play multifaceted roles in cancer progression, including modulation of the tumor microenvironment, facilitation of metastasis, and induction of therapeutic resistance. Their molecular cargo—comprising proteins, lipids, and nucleic acids—serves as a dynamic reflection of the physiological or pathological status of the tumor cells. Technological innovations in exosome isolation, surface modification, and therapeutic payload loading have markedly improved targeted delivery and preclinical treatment outcomes. Notably, drug‑loaded exosomes demonstrate the ability to circumvent multidrug resistance.</div></div><div><h3>Conclusion</h3><div>Exosomes hold substantial promise for precision oncology through enhanced drug delivery and diagnostic applications. However, clinical translation requires standardized manufacturing, comprehensive safety profiling, and scalable production methods to address current limitations. Emerging strategies such as exosome mimetics and AI‑assisted production optimization poised to address these limitations, guiding the development of personalized, efficient, and targeted cancer treatments.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156381"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipokine-mediated crosstalk between metabolic dysregulation and inflammatory pathways","authors":"Zhiheng He ,&nbsp;Linjie Zhao ,&nbsp;Jiarui Liu ,&nbsp;Wanjie Zheng ,&nbsp;Chengjun Gong ,&nbsp;Chengxuan Gong ,&nbsp;Li Guo ,&nbsp;Tingming Liang","doi":"10.1016/j.prp.2025.156312","DOIUrl":"10.1016/j.prp.2025.156312","url":null,"abstract":"<div><div>Adipokines are bioactive signaling molecules secreted by adipose tissue that play crucial roles in the regulation of energy metabolism and inflammatory responses. With the global rise in obesity and related metabolic disorders, understanding adipokine-mediated regulation has become increasingly important for addressing chronic inflammation and its systemic consequences. However, the adipokine-mediated crosstalk between metabolic dysregulation and inflammatory pathways remains incompletely understood. Beyond classical adipokines, adipose tissue-derived microRNAs (miRNAs) have been identified as novel paracrine and endocrine signaling molecules, capable of modulating distant cellular functions through exosome-mediated transport. These extracellular vesicle-encapsulated miRNAs are increasingly recognized as key regulators in inter-organ communication and disease development. This review summarizes the current understanding of adipokine secretion mechanisms, roles in metabolic and inflammatory regulation, and the dual functions in both metabolic diseases and cancer. Emerging therapeutic strategies focusing on targeting adipokines and the signaling pathways downstream are also discussed, highlighting the translational potential of adipokines as promising biomarkers and therapeutic targets for the prevention and treatment of metabolic diseases and cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156312"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145652025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological features and diagnostic challenges of early gastric cardiac carcinoma with dysplastic gastritis cystica profunda: A case report","authors":"Wanlun Wang ,&nbsp;Si Wu ,&nbsp;Jie Luo ,&nbsp;Jiale Ji ,&nbsp;Jianhua Dai ,&nbsp;Senlin Xu","doi":"10.1016/j.prp.2025.156313","DOIUrl":"10.1016/j.prp.2025.156313","url":null,"abstract":"<div><div>Gastric cardiac carcinoma associated with dysplastic gastritis cystica profunda (GCP) with represents a rare clinicopathological entity. Its distinct histological features pose diagnostic challenges, as GCP with mild dysplasia can mimic invasive carcinoma, potentially leading to overdiagnosis, overtreatment, and increased patient morbidity. We report a case of early gastric cardiac carcinoma with dysplastic GCP, treated by endoscopic submucosal dissection (ESD). Histopathological examination revealed a moderately differentiated tubular adenocarcinoma confined to the mucosa, adjacent to submucosal cystic glands exhibiting mild dysplasia, cystic dilation, abundant mucin secretion, and focal mucin pools. Immunohistochemically, the carcinoma was positive for CK7 but negative for MUC2 and MUC5AC, while the cystic glands showed the opposite profile. The Ki67 proliferative index was significantly lower in the cystic glands than in the carcinoma. The final diagnosis was intramucosal moderately differentiated adenocarcinoma of the gastric cardia with mildly dysplastic GCP. No recurrence was observed during the 12-month follow-up. This case highlights the diagnostic pitfalls of this entity, and underscores the importance of accurate pathological recognition to guide clinical management.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156313"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}