PathobiologyPub Date : 2024-01-01Epub Date: 2023-12-21DOI: 10.1159/000535938
Vanesa-Sindi Ivanova, Visar Vela, Stefan Dirnhofer, Michael Dobbie, Frank Stenner, Jan Knoblich, Alexandar Tzankov, Thomas Menter
{"title":"Molecular Characterization and Genetic Subclassification Comparison of Diffuse Large B-Cell Lymphoma: Real-Life Experience with 74 Cases.","authors":"Vanesa-Sindi Ivanova, Visar Vela, Stefan Dirnhofer, Michael Dobbie, Frank Stenner, Jan Knoblich, Alexandar Tzankov, Thomas Menter","doi":"10.1159/000535938","DOIUrl":"10.1159/000535938","url":null,"abstract":"<p><strong>Introduction: </strong>Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity. Lately, several algorithms achieving therapeutically and prognostically relevant DLBCL subclassification have been published.</p><p><strong>Methods: </strong>A cohort of 74 routine DLBCL cases was broadly characterized by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) of the BCL2, BCL6, and MYC loci, and comprehensive high-throughput sequencing (HTS). Based on the genetic alterations found, cases were reclassified using two probabilistic tools - LymphGen and Two-step classifier, allowing for comparison of the two models.</p><p><strong>Results: </strong>Hans and Tally's overall IHC-based subclassification success rate was 96% and 82%, respectively. HTS and FISH data allowed the LymphGen algorithm to successfully classify 11/55 cases (1 - BN2, 7 - EZB, 1 - MCD, and 2 - genetically composite EZB/N1). The total subclassification rate was 20%. On the other hand, the Two-step classifier categorized 36/55 cases, with 65.5% success (9 - BN2, 12 - EZB, 9 - MCD, 2 - N1, and 4 - ST2). Clinical correlations highlighted MCD as an aggressive subtype associated with higher relapse and mortality.</p><p><strong>Conclusions: </strong>The Two-step algorithm has a better success rate at subclassifying DLBCL cases based on genetic differences. Further improvement of the classifiers is required to increase the number of classifiable cases and thus prove their applicability in routine diagnostics.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"245-253"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2024-01-01Epub Date: 2023-11-11DOI: 10.1159/000533745
William Cook, Cheok Soon Lee, Puay Hoon Tan
{"title":"Epithelial Carcinomas Arising within Phyllodes Tumours of the Breast: A Review of Their Pathological Characteristics.","authors":"William Cook, Cheok Soon Lee, Puay Hoon Tan","doi":"10.1159/000533745","DOIUrl":"10.1159/000533745","url":null,"abstract":"<p><p>Epithelial proliferation is a common feature of phyllodes tumours (PTs), but epithelial malignancy is rare. This review seeks to further our understanding of epithelial malignancy within PTs by analysing their histopathological characteristics in previously reported cases and providing an overview of studies on their pathological features. PubMed and DeepDyve were searched for case reports, case series, and literature reviews of in situ and invasive carcinoma within PTs. Only cases where the carcinoma was within the PT were included. Cases of synchronous carcinoma in the ipsilateral or contralateral breast were excluded. Ninety-eight cases of in situ or invasive carcinoma within a PT were identified. Across the grades of PTs, there was a similar proportion of invasive carcinomas compared to in situ lesions. Malignant PT correlates with a higher likelihood of epithelial malignancy, and molecular studies support a possible causal pathophysiological relationship. This higher likelihood may suggest interactions between malignant stroma and the transforming epithelium that could potentially play a significant role in the phenomenon, which remains to be elucidated. Encasement within a PT likely improves the prognosis of breast carcinoma due to earlier detection. The presence of carcinoma within a malignant PT has uncertain prognostic implications. Thorough sampling of all PTs is recommended for appropriate prognostication and management.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"144-157"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89719189","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}
PathobiologyPub Date : 2024-01-01Epub Date: 2023-09-01DOI: 10.1159/000533810
Alexandra Mesquita, Anabela Ferro, José Carlos Machado, Fernando Schmitt
{"title":"Next-Generation Sequencing of Breast Cancer in the Neoadjuvant Setting.","authors":"Alexandra Mesquita, Anabela Ferro, José Carlos Machado, Fernando Schmitt","doi":"10.1159/000533810","DOIUrl":"10.1159/000533810","url":null,"abstract":"<p><strong>Introduction: </strong>Many patients with locally advanced breast cancer are proposed to neoadjuvant chemotherapy (NAT) before surgery. Only some of them achieve a pathological complete response (pCR). The determination of gene somatic alterations using next-generation sequencing (NGS) in the non-pCR tumors is important, in order to identify potential opportunities of treatment for the patients, if targeted therapies are available.</p><p><strong>Methods: </strong>Breast cancer tissue samples of 31 patients, collected before NAT, were analyzed by NGS using the Oncomine™ Comprehensive Assay Plus (OCA-Plus) panel.</p><p><strong>Results: </strong>Twelve patients achieved pCR after NAT. ERBB2 gene alterations were the most frequent in this cohort of pCR patients, followed by BRCA 1 and 2, MYC, TP53, PIK3CA, and MET alterations. Tumors that did not achieve a pCR were mainly triple negative. In this subgroup some BRCA 1 and 2 and PIK3CA gene alterations were identified, as well as TP53 mutations. The NGS panel employed in this study also allowed for the determination of tumor mutation burden (TMB).</p><p><strong>Conclusion: </strong>This study showcases the significance of employing comprehensive genomic testing in breast cancer cases, primarily due to the scarcity of specific target assays. The detection of somatic mutations, coupled with the availability of targeted therapies, holds promise as a potential therapeutic avenue to enhance tumor response rates during NAT, or as a complementary treatment following surgery. Moreover, evaluating the TMB in non-pCR samples could serve as a valuable criterion for selecting patients suitable for immunotherapy. Further exploration through clinical trials is imperative to investigate these prospects.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"114-120"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10145492","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}
PathobiologyPub Date : 2024-01-01Epub Date: 2023-11-01DOI: 10.1159/000534917
Rana Al-Awadhi, Materah Salem Alwehaidah, Moody AlRoomy, Kusum Kapila
{"title":"Relative Telomere Length in Cervical Exfoliated Cells among Women with High-Risk Human Papillomavirus.","authors":"Rana Al-Awadhi, Materah Salem Alwehaidah, Moody AlRoomy, Kusum Kapila","doi":"10.1159/000534917","DOIUrl":"10.1159/000534917","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigates and compares the relative telomere length (RTL) outcome of high-risk (hr) human papillomavirus (HPV)-infected normal, low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL) cervical samples to HPV-free normal cervical samples.</p><p><strong>Methods: </strong>This study used archived cervical samples and obtained cytology and histology data. HPV genotyping was conducted using Sanger sequencing, and RTL was performed using real-time quantitative polymerase chain reaction.</p><p><strong>Results: </strong>This study investigated 287 cervical samples, including 100 normal and hr-HPV-negative samples from the control group, 44 normal and hr-HPV-infected samples, and 143 SIL and hr-HPV-infected samples. The RTL in hr-HPV-infected samples, including the SIL and normal sample groups, was significantly longer than that in the control group. RTL in HSIL (5.13 ± 3.22) and LSIL (2.86 ± 2.81) was significantly different (p < 0.001). The RTL of cervical intraepithelial neoplasia (CIN1) lesion (3.53 ± 2.53) differed significantly (p < 0.001) when compared to CIN2 and CIN3 lesions combined (12.04 ± 10.51). The risk of developing cervical cancer was associated with RTL and decreased with RTL.</p><p><strong>Conclusion: </strong>This study revealed the strong potential of the RTL test in identifying women at risk of developing cervical cancer.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"180-186"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425832","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}
PathobiologyPub Date : 2024-01-01Epub Date: 2023-05-11DOI: 10.1159/000530940
Carlos Faria, Alexandar Tzankov
{"title":"Progression in Myeloid Neoplasms: Beyond the Myeloblast.","authors":"Carlos Faria, Alexandar Tzankov","doi":"10.1159/000530940","DOIUrl":"10.1159/000530940","url":null,"abstract":"<p><p>Disease progression in myelodysplastic syndromes (MDS), myelodysplastic-myeloproliferative neoplasms (MDS/MPN), and myeloproliferative neoplasms (MPN), altogether referred to as myeloid neoplasms (MN), is a major source of mortality. Apart from transformation to acute myeloid leukemia, the clinical progression of MN is mostly due to the overgrowth of pre-existing hematopoiesis by the MN without an additional transforming event. Still, MN may evolve along other recurrent yet less well-known scenarios: (1) acquisition of MPN features in MDS or (2) MDS features in MPN, (3) progressive myelofibrosis (MF), (4) acquisition of chronic myelomonocytic leukemia (CMML)-like characteristics in MPN or MDS, (5) development of myeloid sarcoma (MS), (6) lymphoblastic (LB) transformation, (7) histiocytic/dendritic outgrowths. These MN-transformation types exhibit a propensity for extramedullary sites (e.g., skin, lymph nodes, liver), highlighting the importance of lesional biopsies in diagnosis. Gain of distinct mutations/mutational patterns seems to be causative or at least accompanying several of the above-mentioned scenarios. MDS developing MPN features often acquire MPN driver mutations (usually JAK2), and MF. Conversely, MPN gaining MDS features develop, e.g., ASXL1, IDH1/2, SF3B1, and/or SRSF2 mutations. Mutations of RAS-genes are often detected in CMML-like MPN progression. MS ex MN is characterized by complex karyotypes, FLT3 and/or NPM1 mutations, and often monoblastic phenotype. MN with LB transformation is associated with secondary genetic events linked to lineage reprogramming leading to the deregulation of ETV6, IKZF1, PAX5, PU.1, and RUNX1. Finally, the acquisition of MAPK-pathway gene mutations may shape MN toward histiocytic differentiation. Awareness of all these less well-known MN-progression types is important to guide optimal individual patient management.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"55-75"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10857805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9524167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2024-01-01Epub Date: 2023-06-13DOI: 10.1159/000531480
Yen-Chun Liu, Julia T Geyer
{"title":"Pediatric Hematopathology in the Era of Advanced Molecular Diagnostics: What We Know and How We Can Apply the Updated Classifications.","authors":"Yen-Chun Liu, Julia T Geyer","doi":"10.1159/000531480","DOIUrl":"10.1159/000531480","url":null,"abstract":"<p><p>Pediatric hematologic malignancies often show genetic features distinct from their adult counterparts, which reflect the differences in their pathogenesis. Advances in the molecular diagnostics including the widespread use of next-generation sequencing technology have revolutionized the diagnostic workup for hematologic disorders and led to the identification of new disease subgroups as well as prognostic information that impacts the clinical treatment. The increasing recognition of the importance of germline predisposition in various hematologic malignancies also shapes the disease models and management. Although germline predisposition variants can occur in patients with myelodysplastic syndrome/neoplasm (MDS) of all ages, the frequency is highest in the pediatric patient population. Therefore, evaluation for germline predisposition in the pediatric group can have significant clinical impact. This review discusses the recent advances in juvenile myelomonocytic leukemia, pediatric acute myeloid leukemia, B-lymphoblastic leukemia/lymphoma, and pediatric MDS. This review also includes a brief discussion of the updated classifications from the International Consensus Classification (ICC) and the 5th edition World Health Organization (WHO) classification regarding these disease entities.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"30-44"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10857803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9627352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2024-01-01Epub Date: 2023-02-15DOI: 10.1159/000529701
Leander van Eekelen, Geert Litjens, Konnie M Hebeda
{"title":"Artificial Intelligence in Bone Marrow Histological Diagnostics: Potential Applications and Challenges.","authors":"Leander van Eekelen, Geert Litjens, Konnie M Hebeda","doi":"10.1159/000529701","DOIUrl":"10.1159/000529701","url":null,"abstract":"<p><p>The expanding digitalization of routine diagnostic histological slides holds a potential to apply artificial intelligence (AI) to pathology, including bone marrow (BM) histology. In this perspective, we describe potential tasks in diagnostics that can be supported, investigations that can be guided, and questions that can be answered by the future application of AI on whole-slide images of BM biopsies. These range from characterization of cell lineages and quantification of cells and stromal structures to disease prediction. First glimpses show an exciting potential to detect subtle phenotypic changes with AI that are due to specific genotypes. The discussion is illustrated by examples of current AI research using BM biopsy slides. In addition, we briefly discuss current challenges for implementation of AI-supported diagnostics.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"8-17"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10731444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2024-01-01Epub Date: 2023-03-30DOI: 10.1159/000530431
Tayler A van den Akker, Yen-Chun Liu, Huifei Liu, Jennifer Chapman, Jennifer M Levine, Olga K Weinberg, Julia T Geyer
{"title":"Myeloid Proliferations Associated with Down Syndrome: Clinicopathologic Characteristics of Forty Cases from Five Large Academic Institutions.","authors":"Tayler A van den Akker, Yen-Chun Liu, Huifei Liu, Jennifer Chapman, Jennifer M Levine, Olga K Weinberg, Julia T Geyer","doi":"10.1159/000530431","DOIUrl":"10.1159/000530431","url":null,"abstract":"<p><strong>Introduction: </strong>The incidence of myelodysplastic syndrome and acute myeloid leukemia is significantly increased in children with Down syndrome (DS). Within the revised 2016 WHO edition, these entities are jointly classified as myeloid leukemia associated with DS (ML-DS). Additionally, infants with DS may develop transient abnormal myelopoiesis (TAM) which is histomorphologically similar to ML-DS. While TAM is self-limiting, it is associated with an increased risk of subsequently developing ML-DS. Differentiating TAM and ML-DS is challenging but clinically critical.</p><p><strong>Methods: </strong>We performed a retrospective review of ML-DS and TAM cases collected from five large academic institutions in the USA. We assessed clinical, pathological, immunophenotypical, and molecular features to identify differentiating criteria.</p><p><strong>Results: </strong>Forty cases were identified: 28 ML-DS and 12 TAM. Several features were diagnostically distinct, including younger age in TAM (p < 0.05), as well as presentation with clinically significant anemia and thrombocytopenia in ML-DS (p < 0.001). Dyserythropoiesis was unique to ML-DS, as well as structural cytogenetic abnormalities aside from the constitutional trisomy 21. Immunophenotypic characteristics of TAM and ML-DS were indistinguishable, including the aberrant expression of CD7 and CD56 by the myeloid blasts.</p><p><strong>Discussion: </strong>The findings of the study confirm marked biological similarities between TAM and ML-DS. At the same time, several significant clinical, morphological, and genetic differences were observed between TAM and ML-DS. The clinical approach and the differential diagnosis between these entities are discussed in detail.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"89-98"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10857798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9227429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2024-01-01Epub Date: 2024-05-08DOI: 10.1159/000539010
Yi Pan, Hongtian Dai, Shuhao Wang, Lang Wang, Qiting Li, Wenmiao Wang, Jiangtao Li, Dan Qi, Zhaoyang Yang, Jia Jia, Yaxi Wang, Qing Fang, Lin Li, Weixun Zhou, Zhigang Song, Shuangmei Zou
{"title":"Clinically Applicable Pan-Origin Cancer Detection for Lymph Nodes via Artificial Intelligence-Based Pathology.","authors":"Yi Pan, Hongtian Dai, Shuhao Wang, Lang Wang, Qiting Li, Wenmiao Wang, Jiangtao Li, Dan Qi, Zhaoyang Yang, Jia Jia, Yaxi Wang, Qing Fang, Lin Li, Weixun Zhou, Zhigang Song, Shuangmei Zou","doi":"10.1159/000539010","DOIUrl":"10.1159/000539010","url":null,"abstract":"<p><strong>Introduction: </strong>Lymph node metastasis is one of the most common ways of tumour metastasis. The presence or absence of lymph node involvement influences the cancer's stage, therapy, and prognosis. The integration of artificial intelligence systems in the histopathological diagnosis of lymph nodes after surgery is urgent.</p><p><strong>Methods: </strong>Here, we propose a pan-origin lymph node cancer metastasis detection system. The system is trained by over 700 whole-slide images (WSIs) and is composed of two deep learning models to locate the lymph nodes and detect cancers.</p><p><strong>Results: </strong>It achieved an area under the receiver operating characteristic curve (AUC) of 0.958, with a 95.2% sensitivity and 72.2% specificity, on 1,402 WSIs from 49 organs at the National Cancer Center, China. Moreover, we demonstrated that the system could perform robustly with 1,051 WSIs from 52 organs from another medical centre, with an AUC of 0.925.</p><p><strong>Conclusion: </strong>Our research represents a step forward in a pan-origin lymph node metastasis detection system, providing accurate pathological guidance by reducing the probability of missed diagnosis in routine clinical practice.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"345-358"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892189","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":"IQ Motif Containing GTPase-Activating Protein 3 Is Associated with Cancer Stemness and Survival in Pancreatic Ductal Adenocarcinoma.","authors":"Aya Kido, Akira Ishikawa, Takafumi Fukui, Narutaka Katsuya, Kazuya Kuraoka, Kazuhiro Sentani, Sho Tazuma, Takeshi Sudo, Masahiro Serikawa, Shiro Oka, Naohide Oue, Wataru Yasui","doi":"10.1159/000535542","DOIUrl":"10.1159/000535542","url":null,"abstract":"<p><strong>Introduction: </strong>Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of malignancy, with poor prognosis and rising incidence. IQ motif containing GTPase-activating protein 3 (IQGAP3) is a member of the IQGAPs family of scaffolding proteins that govern multiple cellular activities like cytoskeletal remodeling and cellular signal transduction. This study aimed to analyze the expression and biological function of IQGAP3 in PDAC.</p><p><strong>Methods: </strong>We analyzed IQGAP3 expression in 81 PDAC samples by immunohistochemistry. RNA interference was used to inhibit IQGAP3 expression in PDAC cell lines.</p><p><strong>Results: </strong>Immunohistochemical analysis of IQGAP3 showed that 54.3% of PDACs were positive for cytoplasmic expression of IQGAP3, with no expression found in non-neoplastic tissue. Furthermore, IQGAP3 expression was an independent poor prognostic factor in our immunostaining-based studies and analyses of public databases. Our cohort and the Cancer Genome Atlas database indicated that IQGAP3 is co-localized with kinesin family member C1 (KIFC1), which we previously reported as a cancer stem cell-associated protein. IQGAP3 small interfering RNA treatment decreased PDAC cell proliferation and spheroid colony formation via ERK and AKT pathways.</p><p><strong>Discussion/conclusion: </strong>These results suggest that IQGAP3, a transmembrane protein, is involved in survival and stemness and may be a promising new therapeutic target for PDAC.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"268-278"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}