Laboratory Investigation最新文献

{"title":"Role of Reserve Cells in Metaplasia and the Development of Human Papillomavirus–Associated High-Grade Squamous Intraepithelial Lesions at the Cervical Transformation Zone","authors":"Ademola Aiyenuro ,&nbsp;Heather Griffin ,&nbsp;Konstanze Schichl ,&nbsp;Tanvier Omar ,&nbsp;Jaume Ordi ,&nbsp;Helen Kelly ,&nbsp;Caroline Walker ,&nbsp;Marta del Pino ,&nbsp;Kanan Desai ,&nbsp;Silvia de Sanjosé ,&nbsp;Mark Schiffman ,&nbsp;John Doorbar","doi":"10.1016/j.labinv.2025.104166","DOIUrl":"10.1016/j.labinv.2025.104166","url":null,"abstract":"<div><div>Squamous cervical cancers generally arise as a result of persistent infection with high-risk human papillomaviruses (hrHPVs) and occur near the squamocolumnar junction (SCJ) and within the transformation zone (TZ). The susceptibility of the TZ to HPV-related carcinogenesis appears linked to epithelial cell plasticity, with squamous metaplasia originating from a specialized stem cell population at this site. Two alternative cell populations have been implicated: keratin (K)7+ve cuboidal cells located at the SCJ vs a more broadly distributed K17+ve cervical reserve cell population. To distinguish between the hypotheses, we utilized multiplex immunofluorescence and large-scale digital imaging to map cell populations at the TZ of 165 women with and without hrHPV infections. Our results did not reveal a distinct population of K7+ cuboidal cells at the SCJ but found instead that the cuboidal and columnar cells of the TZ express K7 and K8 throughout and lack the p63 transcription factor required for epithelial stratification. Squamous metaplasia and reserve cells, which are defined by their subcolumnar location and pattern of biomarker expression (K5/K17/P63), were conspicuous at cervical crypt entrances within the TZ extending proximally toward the endocervix. In HPV-infected tissue, crypt-entrance regions with thin high-grade squamous intraepithelial lesion pathology showed prominent expression of hrHPV E6/E7 mRNA, as detected by fluorescence in situ hybridization, and p16/MCM expression, with infection also apparent in neighboring reserve cells. In some instances, normal/uninfected reserve cells (E6/E7 mRNA−ve) and squamous metaplasia were not only seen close to these regions of hrHPV infection but also extended well beyond the infected area both laterally and by depth. Our results confirm that the reserve cells underneath the columnar epithelia at TZ have the potential to undergo malignant squamous transformation via reserve cell proliferation, in agreement with previous histopathological studies. These translational findings highlight the importance of understanding the molecular biology of the epithelial sites where HPV cancers develop and suggest that in high-risk individuals, treatment strategies should target a wider area than previously thought.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 7","pages":"Article 104166"},"PeriodicalIF":5.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflamed Intestinal Epithelial Cells From Patients With Ulcerative Colitis Restore a Noninflamed Transcriptional Profile Upon In Vitro Expansion","authors":"Alexander Due Hammerhøj ,&nbsp;Theresa Louise Boye ,&nbsp;Jiayi Yao ,&nbsp;Annika Hausmann ,&nbsp;Lauge Kellermann ,&nbsp;Grzegorz Jerzy Maciag ,&nbsp;Albin Sandelin ,&nbsp;Casper Steenholdt ,&nbsp;Kim Bak Jensen ,&nbsp;Ole Haagen Nielsen","doi":"10.1016/j.labinv.2025.104172","DOIUrl":"10.1016/j.labinv.2025.104172","url":null,"abstract":"<div><div>Ulcerative colitis (UC) is characterized by chronic relapsing inflammation starting from the rectum and distal colon, which in severe disease cases may affect the entire colon. Intestinal stem cells (ISCs) directly isolated from inflamed UC colonic tissue specimens have been found to present an inflammatory gene expression profile. However, a critical issue is whether these cells retain memory of exposure to inflammation and/or therapeutics. Here, we aimed to investigate whether human intestinal epithelial cells retain the inflammatory state observed in vivo when expanded in vitro as 3D cultured organoids to assess their suitability for therapeutic transplantation. ISCs were isolated from noninflammatory bowel disease controls (noninflamed; n = 18), as well as from colonoscopy-obtained biopsies of the sigmoid colon from individuals diagnosed with UC (inflamed), who were glucocorticoid naïve (n = 19). Moreover, ISCs were collected from all patients with inflammatory bowel disease following prednisolone treatment. Epithelial cells were cultured as 3D intestinal organoids in media to support stem cell maintenance and differentiation. Subsequently, the 3D intestinal organoids were harvested at the end of passage 2 for bulk RNA sequencing. The data revealed that the cellular phenotype of in vitro–cultured epithelial cells isolated from inflamed tissue did not maintain the hallmarks of inflammation observed in the ulcerated environment from which the cells were initially obtained. Our findings indicate that the autologous reinsertion of in vitro–expanded ISCs in active stages of UC may aid in intestinal healing, which calls for future clinical studies. Additionally, a link between organoid morphology and the inflammatory state of the tissue of origin was identified, as organoids derived from inflamed colon exhibited a lower degree of circularity.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 7","pages":"Article 104172"},"PeriodicalIF":5.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Value of PARP1 and PARP2 Copy Number Alterations in Prostate Cancer","authors":"Laura Segalés ,&nbsp;Joaquim Bellmunt ,&nbsp;Júlia Perera-Bel ,&nbsp;Gardenia Vargas-Parra ,&nbsp;Nuria Juanpere ,&nbsp;David López ,&nbsp;Alejo Rodriguez-Vida ,&nbsp;Lluís Colomo ,&nbsp;Lluís Cecchini ,&nbsp;Josep Lloreta-Trull ,&nbsp;José Yélamos ,&nbsp;Lluís Fumadó ,&nbsp;Silvia Hernández-Llodrà","doi":"10.1016/j.labinv.2025.104171","DOIUrl":"10.1016/j.labinv.2025.104171","url":null,"abstract":"<div><div>PARP1/2 have overlapping yet nonredundant biological functions in DNA repair and androgen receptor-transcriptional regulation. Studies on PARP alterations in human tumors have yielded conflicting results. In prostate cancer (PCa), PARP1/2 protein overexpression has been related to androgen deprivation therapy resistance, biochemical recurrence, and progression to metastases. PARP inhibitors have been approved for treating metastatic castration-resistant PCa with homologous recombination repair gene mutations. However, the significance of <em>PARP1/2</em> genomic alterations is not fully studied. We aimed to analyze <em>PARP1/2</em> alterations in PCa, assess their value as prognostic markers, and explore their relevance for potential therapeutic stratification. <em>PARP1</em>/<em>2</em> copy number status was evaluated in 121 PCa primary tumors using real-time PCR. In 29 of them, a regional pelvic lymph node involvement was also analyzed. <em>BRCA1</em>/<em>2</em> somatic mutations were analyzed in 24 PCa cases. Relationship with clinicopathological features, progression to metastases, and prostate-specific antigen recurrence was assessed. <em>PARP1</em> loss and <em>PARP2</em> gain were detected in 34.7% and 32.2% of primary tumors, respectively, with a high frequency of co-occurrence (<em>P</em> &lt; .001). Both alterations were statistically associated with locally advanced disease at the time of diagnosis (<em>P</em> = .036; <em>P</em> = .006), metastatic dissemination (<em>P</em> = .014; <em>P</em> = .003), and other aggressive clinicopathological characteristics (such as the presence of Gleason pattern 5, high-grade, and high-stage). Cases with exclusive <em>PARP2</em> gain had the shortest time to prostate-specific antigen recurrence, whereas double <em>wt</em> patients displayed the best outcome (<em>P</em> = .007). In 29 paired primary tumors and regional pelvic lymph node involvement, <em>PARP1</em> loss showed strong concordance (<em>P</em> = .001), whereas <em>PARP2</em> gain did not (<em>P</em> = .411). In conclusion, loss of <em>PARP1</em> and gain of <em>PARP2</em> show strong co-occurrence and are associated with clinicopathological characteristics of aggressiveness. <em>PARP2</em> alterations appear to have a particularly significant impact on disease prognosis. Furthermore, these data suggest that the analysis of <em>PARP1/2</em> copy number status could be useful in predicting PCa outcomes. Its role in therapy warrants further evaluation.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 6","pages":"Article 104171"},"PeriodicalIF":5.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Epstein-Barr Virus–Encoded Latent Membrane Protein 2A Promotes Immune Escape by Upregulating SYK/Nuclear Factor-κB Signaling in Diffuse Large B-cell Lymphoma” [Laboratory Investigation 105 (2025) 104104]","authors":"Xiang-Nan Jiang ,&nbsp;Dong Sheng ,&nbsp;Wan-Hui Yan ,&nbsp;Xiao-Jie Li ,&nbsp;Qing-Xin Xia ,&nbsp;Xiao-Qiu Li","doi":"10.1016/j.labinv.2025.104164","DOIUrl":"10.1016/j.labinv.2025.104164","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 5","pages":"Article 104164"},"PeriodicalIF":5.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mild Duodenal Mucosal Injury and Increased Type I Interferon Signaling Are Preludes to Celiac Disease","authors":"Changqing Ma ,&nbsp;Adina K. Bard ,&nbsp;Eric Tycksen ,&nbsp;Brian D. Muegge ,&nbsp;Phillip I. Tarr ,&nbsp;Lori R. Holtz ,&nbsp;Ta-Chiang Liu","doi":"10.1016/j.labinv.2025.104170","DOIUrl":"10.1016/j.labinv.2025.104170","url":null,"abstract":"<div><div>Celiac disease (CeD) is an immune-mediated chronic enteropathy caused by gluten exposure in genetically susceptible individuals. The characteristic histologic features of CeD include increased intraepithelial lymphocytes and villous atrophy. Clinically, a subset of individuals with elevated concentrations of serum tissue transglutaminase (TTG) antibodies have intact duodenal villous architecture at initial endoscopy and biopsy but then progress to CeD over time while on gluten-containing foods. We hypothesized that these rare potential CeD cases with progression can allow us to interrogate histologic and molecular signatures to predict those who subsequently develop CeD and to study the final cascade into the overt lesions of CeD. We retrospectively identified 16 children over a 10-year period with elevated serum TTG antibody concentrations but without significant villous atrophy at index duodenal biopsies, in whom subsequent biopsies confirmed CeD while consuming gluten-containing foods. Their clinical and histologic features were compared with age-, race-, and gender-matched controls including active CeD (n = 28) and non-CeD children (negative TTG antibody, normal histology, n = 35). Transcriptomic analysis was performed on a subset of the index biopsies of potential CeD cases with progression and controls. None of the 16 children with potential CeD with progression had a family history of CeD or presented with poor growth or anemia or had commenced a gluten-free diet at the time of index biopsy. The index biopsies of children with potential CeD with progression had significantly greater prevalence of intraepithelial lymphocytes (81% vs 12%, <em>P</em> = .002) and mild villous atrophy (94% vs 22%, <em>P</em> = .006) compared with non-CeD biopsies; none had severe villous atrophy (<em>P</em> = .002). Transcriptomic analysis demonstrated upregulated type I interferon signaling, Janus kinase (JAK)/signal transducer and activator (STAT) pathway of transcription activation and innate and adaptive immunity in duodenum of potential CeD with progression was comparable to non-CeD but preserved signaling in brush border absorption, transporter functions, and epithelial metabolic functions, compared with active CeD. Our results show for the first time that mild mucosal injury in the duodenum of children with potential CeD with progression is accompanied by upregulation of pathways also activated in CeD. Mild mucosal injury and type I interferon signaling may be the initiating cellular and molecular biomarkers in identifying the subset of potential CeD individuals who would progress to CeD while consuming gluten-containing foods.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 7","pages":"Article 104170"},"PeriodicalIF":5.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Fluorescence In Situ Hybridization, Next-Generation Sequencing, and DNA Methylation Microarray for Copy Number Variation Assessment in Gliomas","authors":"Jiao Wang ,&nbsp;Yang Lan ,&nbsp;Hao-Yue Qi ,&nbsp;Li-Hong Wang ,&nbsp;Sen Wei ,&nbsp;Ye Yuan ,&nbsp;Jia Ge ,&nbsp;Ai-Ling Li ,&nbsp;Ze-Xuan Yan ,&nbsp;Lei Li ,&nbsp;Peng-Yu Ming ,&nbsp;Tian-Ran Hu ,&nbsp;Xiu-Wu Bian ,&nbsp;Xiao-Hong Yao ,&nbsp;Tao Luo","doi":"10.1016/j.labinv.2025.104168","DOIUrl":"10.1016/j.labinv.2025.104168","url":null,"abstract":"<div><div>Gene-level and chromosomal copy number variation (CNV) assessments are critical in the integrated diagnosis of gliomas. Whereas fluorescence in situ hybridization (FISH) has been traditionally employed for CNV detection, emerging technologies such as next-generation sequencing (NGS) and DNA methylation microarray (DMM) are available in clinical practice. Nevertheless, the comparative performance of these 3 assays and the concordance of them remain unclear. A retrospective cohort study comprising 104 patients diagnosed with gliomas was conducted at our hospital. We systematically compared FISH, NGS, and DMM for detecting the following 6 CNV-related diagnostic or prognostic parameters: epidermal growth factor receptor (<em>EGFR</em>), cyclin-dependent kinase inhibitor 2A/B (<em>CDKN2A/B</em>), 1p, 19q, chromosome 7, and chromosome 10. All the 3 methods showed high consistency in <em>EGFR</em> assessment; however, FISH demonstrated relatively low concordance with NGS/DMM in detecting other parameters. In contrast, NGS and DMM exhibited strong concordance in the assessment of all the 6 parameters. Notably, discordant cases were associated with high-grade gliomas (grade 3/4; <em>P</em> &lt; .05) and a high fraction of genome altered (<em>P</em> &lt; .01), indicating high malignancy and genomic instability of discordant cases. This study elucidated the discrepancies and limitations of conventional FISH compared with NGS/DMM in CNV assessments. The discrepancies were associated with high-grade gliomas and genomic instability. We propose a process with recommendations on methods, highlighting the importance of integrated multiplatform assays in accurate clinical diagnosis.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 7","pages":"Article 104168"},"PeriodicalIF":5.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APOBEC-Driven Hypermutation in the Lymphocyte-Predominant Group of Triple-Negative Breast Cancer","authors":"Miseon Lee ,&nbsp;Ahwon Lee ,&nbsp;Tae-Kyung Yoo ,&nbsp;Byung Joo Chae ,&nbsp;Sung Gwe Ahn ,&nbsp;Byung-Ock Choi ,&nbsp;Woo-Chan Park ,&nbsp;Sung Hun Kim ,&nbsp;Jieun Lee ,&nbsp;Jun Kang","doi":"10.1016/j.labinv.2025.104165","DOIUrl":"10.1016/j.labinv.2025.104165","url":null,"abstract":"<div><div>This study aimed to evaluate the clinicopathologic and genomic characteristics of triple-negative breast cancer subclassification. Triple-negative breast cancer was classified into the luminal androgen receptor (LAR) subtype and the tumor-infiltrating lymphocytes (TILs) groups of the non-LAR subtype—lymphocyte predominant (LP), lymphocyte intermediate, and lymphocyte depleted—based on androgen receptor immunohistochemistry and TILs. Clinicopathologic and genomic characteristics were evaluated for these triple-negative breast cancer subclasses. The LP group was associated with a histologic type of carcinoma with medullary features, a higher tumor mutation burden, and increased APOBEC activity, indicative of APOBEC-driven hypermutation. The LAR subtype was characterized by a higher prevalence of <em>PIK3CA</em> mutations, lower homologous recombination deficiency scores, and associations with histologic types of invasive lobular carcinoma, and carcinoma with apocrine differentiation. This study demonstrated the distinct clinicopathologic and genomic characteristics of triple-negative breast cancer subclassifications. APOBEC activity–related hypermutation is a defining characteristic of the LP group.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 7","pages":"Article 104165"},"PeriodicalIF":5.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hidden in the Absence: Clinicopathologic Insights on Kidney Diseases Associated With Selective IgA Deficiency","authors":"Bangchen Wang ,&nbsp;Harpreet Singh ,&nbsp;Matthew Ellis ,&nbsp;Laura Barisoni ,&nbsp;David N. Howell","doi":"10.1016/j.labinv.2025.104163","DOIUrl":"10.1016/j.labinv.2025.104163","url":null,"abstract":"<div><div>Selective IgA deficiency (sIgAD) is the most common type of primary immunodeficiency. The diagnosis of sIgAD has occasionally been suggested when a complete absence of background IgA immunofluorescent staining on renal biopsies was observed, but such findings have been described in only 2 patients to date. In this study, the clinical, demographic, and renal biopsy findings of 15 patients with suspected sIgAD, based on a total lack of immunofluorescence for IgA, were collected. In our cohort, most patients presented with acute kidney injury, with or without proteinuria, and had clinical histories consistent with sIgAD, including recurrent infections, autoimmune diseases, allergic disorders, and cancer. However, only 1 patient had a known history of sIgAD. Immunoglobulin testing was available in 10 of 15 patients, 9 of whom showed findings consistent with a diagnosis of sIgAD. Renal biopsies in most patients revealed immune-related glomerular diseases, with lupus nephritis being the most common diagnosis. Recognizing the total absence of IgA staining indicative of sIgAD is important because it can be associated with recurrent infections, autoimmune diseases, allergic disorders, anaphylactic transfusion reactions, and, rarely, malignancies.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 7","pages":"Article 104163"},"PeriodicalIF":5.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover","authors":"","doi":"10.1016/S0023-6837(25)00042-X","DOIUrl":"10.1016/S0023-6837(25)00042-X","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 4","pages":"Article 104132"},"PeriodicalIF":5.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant Therapy–Associated CDX2 Expression and Its Prognostic Implication in Esophageal Adenocarcinoma","authors":"Heong Ahn ,&nbsp;Madhurya Ramineni ,&nbsp;Hangchuan Shi ,&nbsp;Rena X. Li ,&nbsp;Moises Velez ,&nbsp;Yansheng Hao","doi":"10.1016/j.labinv.2025.104135","DOIUrl":"10.1016/j.labinv.2025.104135","url":null,"abstract":"<div><div>Neoadjuvant chemoradiotherapy followed by surgery is the standard care for locally advanced esophageal adenocarcinoma. However, reliable postoperative prognostic biomarkers are still needed to stratify patients with different clinical outcomes. This study aimed to investigate postneoadjuvant expression changes of CDX2 and its association with histopathological features, biomarkers for targeted therapy, distant metastasis, and survival status. A total of 62 esophagogastrectomy specimens from one institution were evaluated. A tissue microarray was constructed, and IHC staining was performed. CDX2 expression was found in 27 (43.5%) cases with well-to-poor differentiation. Compared with preoperative biopsies, 68.8% of cases demonstrated induced or enhanced CDX2 expression. There were no significant differences in age, tumor location, histologic grade, lymph node metastasis, tumor stage, and treatment response between CDX2-positive and CDX2-negative groups. Neuroendocrine and Paneth cell differentiation induced by neoadjuvant therapy were more commonly seen in CDX2-positive cases. CDX2 expression was associated with higher multidrug resistance-1 and HER-2 expression. Patients with CDX2-positive diseases showed a higher risk of distant metastasis and a worse prognosis than those with CDX2-negative diseases.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 6","pages":"Article 104135"},"PeriodicalIF":5.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}