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Trop2-Expression in Correlation to the Molecular Subtype in Vulvar Squamous Cell Carcinomas (VSCC). 外阴鳞状细胞癌(VSCC)分子亚型与trop2表达的关系
IF 3.5 4区 医学
Pathobiology Pub Date : 2025-01-21 DOI: 10.1159/000543554
Anne Kathrin Höhn, Benjamin Wolf, Mirjam Forberger, Christine E Brambs, Blake Gilks, Lien Hoang, Grit Gesine Ruth Hiller, Jessica N McAlpine, Amy Jamieson, Yvette Drew, Lars-Christian Horn
{"title":"Trop2-Expression in Correlation to the Molecular Subtype in Vulvar Squamous Cell Carcinomas (VSCC).","authors":"Anne Kathrin Höhn, Benjamin Wolf, Mirjam Forberger, Christine E Brambs, Blake Gilks, Lien Hoang, Grit Gesine Ruth Hiller, Jessica N McAlpine, Amy Jamieson, Yvette Drew, Lars-Christian Horn","doi":"10.1159/000543554","DOIUrl":"https://doi.org/10.1159/000543554","url":null,"abstract":"<p><p>Targeted therapy with antibody-drug conjugates (ADCs) has shown promising results in the treatment of various solid tumours. Sacituzumab-govitecan (SG), a humanised anti-Trop2 monoclonal antibody in combination with the cytotoxic topoisomerase I inhibitor SN38, has been approved for the treatment of metastatic triple-negative breast cancer. The treatment approach with SG requires the expression of Trop2 in the tumour cells. Trop2 is overexpressed in many other cancers, suggesting a broader therapeutic application of these ADCs beyond breast cancer. We are investigating the expression of Trop2 in vulvar squamous cell carcinoma (VSCC) and how this relates to molecular classification. Immunohistochemical Trop2 expression was assessed in diagnostic biopsies of VSCC using an immunoreactive score. The staining results were compared with the molecular subtype of VSCC. 57 cases were included in the study. 63.2% of VSCC were 16-ve/p53abn (HPV-independent (p53abn)) molecular subtype, 29.8% p16+ve/p53wt (HPV-associated) and 1.4% p16-ve/p53wt-(HPV-independent (p53wt)) tumors. All diagnostic biopsies (N=57) showed at least weak Trop2-expression. Expression was significantly higher, as assessed by an immunreactive score, in the HPV-associated VSCC, compared to HPV-independent. VSCC have high expression of Trop2 and represents a promising therapeutic target. Clinical trials exploring Trop2 directed ADCs such as Sacituzumab-Govitecan are warranted in this rare cancer type, including in the prognostically poor HPV-independent VSCC with a TP53-mutation (p16-ve/p53abn molecular subtype). The targetable molecule Trop2 can be easily assessed by immunohistochemistry on diagnostic biopsies from VSCC. ree version).</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-12"},"PeriodicalIF":3.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009448","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}
引用次数: 0
Gastric adenocarcinoma with enteroblastic differentiation. 胃腺癌伴肠母细胞分化。
IF 3.5 4区 医学
Pathobiology Pub Date : 2025-01-07 DOI: 10.1159/000543330
Ádám Ferenczi, Levente Kuthi, Anita Sejben
{"title":"Gastric adenocarcinoma with enteroblastic differentiation.","authors":"Ádám Ferenczi, Levente Kuthi, Anita Sejben","doi":"10.1159/000543330","DOIUrl":"https://doi.org/10.1159/000543330","url":null,"abstract":"<p><strong>Introduction: </strong>Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare entity with worse prognosis compared to conventional gastric adenocarcinomas. Its histological characteristics are fetal gut-like architecture and tumor cells with cytoplasmic clearing, as well as positive immunohistochemical reaction to at least one of the enteroblastic markers. Hereby, we present a case of GAED with neuroendocrine marker positivity, with whole exome sequencing (WES), and an updated literature review.</p><p><strong>Case presentation: </strong>A 68-year-old woman presented with abdominal pain. Gastric wall thickening raised suspicion of gastric cancer, thus gastroscopy was performed, and biopsy samples were taken, which confirmed malignancy. Neoadjuvant systemic chemotherapy was initiated, and total gastrectomy was performed. Microscopically, pleomorphic polygonal cells were visible with clear cytoplasm and high grade cellular atypia. Alcian blue and PAS stains demonstrated positivity for acidic and neutral mucins. P53 IHC was negative, indicative of null-phenotype, while Syntaxin-1 and Chromogranin showed focal positivity. SALL4 and Glypican 3 were positive, however, AFP displayed only minimal, uncertain positivity. The Ki67 labeling index was 70%. Due to the morphological and immunohistochemical characteristics, the tumor was concluded as GAED with neuroendocrine marker positivity. WES was carried out revealing 4 pathogenic, including TP53, KLHL7, RAPSN, and ACTA1, and 3 likely pathogenic mutations, encompassing PNKP, HNF1A, and ADNP.</p><p><strong>Discussion: </strong>GAED is a rare subtype of gastric adenocarcinomas, representing 0.3-5.4% of all cases and has an unclarified etiology. Our WES results identified new pathogenic and likely pathogenic mutations. From a differential diagnostic point of view, hepatoid adenocarcinoma, and the possibility of metastatic origin has to be excluded.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-24"},"PeriodicalIF":3.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952803","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}
引用次数: 0
Metabolic Analysis of Three-Dimensional Cultured Gastrointestinal Cancer Cells Suggests that l-Arginine Inhibits Tumor Growth by Affecting the Urea Cycle. 三维培养胃肠道癌细胞的代谢分析表明,l -精氨酸通过影响尿素循环抑制肿瘤生长。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-12-10 DOI: 10.1159/000543006
Eri Tanaka, Naoko Taniura, Ken-Ichi Mukaisho, Yusuke Kageyama, Mai Noujima, Hirohito Ishigaki, Takahisa Nakayama, Ryoji Kushima
{"title":"Metabolic Analysis of Three-Dimensional Cultured Gastrointestinal Cancer Cells Suggests that <sc>l</sc>-Arginine Inhibits Tumor Growth by Affecting the Urea Cycle.","authors":"Eri Tanaka, Naoko Taniura, Ken-Ichi Mukaisho, Yusuke Kageyama, Mai Noujima, Hirohito Ishigaki, Takahisa Nakayama, Ryoji Kushima","doi":"10.1159/000543006","DOIUrl":"10.1159/000543006","url":null,"abstract":"<p><strong>Introduction: </strong>There is evidence for the anticancer effects of <sc>l</sc>-arginine (arginine); however, the direct effects on cancer cells and mechanism of action are unclear.</p><p><strong>Methods: </strong>Various upper gastrointestinal cancer cells (OE19, OE33, MKN1, MKN45, MKN74, and AGS) were divided into arginine-treated and -untreated groups and cultured using two-dimensional and three-dimensional culture systems. Proliferation was evaluated using the MTT assay to identify arginine-sensitive (OE33) and arginine-insensitive (OE19) strains. Furthermore, the effects of arginine were evaluated using a mitochondrial stress test, cell cycle assay, comprehensive metabolic analysis, and tracer study using (13C6) <sc>l</sc>-arginine.</p><p><strong>Results: </strong>In OE33 (but not in OE19), the maximal respiratory capacity of mitochondria was lower in the treated group than in the control group. In OE33, S phase cells (determined using BrdU) were significantly reduced. In a comprehensive metabolic analysis of OE33, citrulline/ornithine levels were significantly lower in arginine-treated than in untreated cells. Using OE33, carbamoyl aspartic acid (CAA) levels were significantly lower in arginine-treated than in untreated cells. A tracer study suggested that arginine promotes the urea cycle.</p><p><strong>Conclusion: </strong>Arginine affected urea cycle metabolism, thereby decreasing CAA, which is required for pyrimidine nucleotide synthesis. These findings provide insight into the mechanism underlying the anticancer effects of arginine.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-17"},"PeriodicalIF":3.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807750","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}
引用次数: 0
Roles of Cancer Histology Type and HPV Genotype in HPV ctDNA Detection at Baseline in Cervical Cancer: Implications for Tumor Burden Assessment. 宫颈癌基线 HPV ctDNA 检测中癌症组织学类型和 HPV 基因型的作用:对肿瘤负担评估的影响。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-11-27 DOI: 10.1159/000542638
Miseon Lee, Eun Ji Lee, Jun Kang, Keun Ho Lee, Sung Jong Lee, Sook Hee Hong, Hee Seung Kim, Ahwon Lee
{"title":"Roles of Cancer Histology Type and HPV Genotype in HPV ctDNA Detection at Baseline in Cervical Cancer: Implications for Tumor Burden Assessment.","authors":"Miseon Lee, Eun Ji Lee, Jun Kang, Keun Ho Lee, Sung Jong Lee, Sook Hee Hong, Hee Seung Kim, Ahwon Lee","doi":"10.1159/000542638","DOIUrl":"10.1159/000542638","url":null,"abstract":"<p><strong>Introduction: </strong>Human papillomavirus circulating tumor DNA (HPV ctDNA) is a promising biomarker for monitoring cervical cancer. HPV ctDNA level at baseline (before treatment) reflects tumor burden. However, reported HPV ctDNA detection rates at baseline have shown variations across studies, suggesting the existence of other potential contributing factors. This study aimed to identify additional factors that might influence HPV ctDNA detection at baseline, focusing on histology type and HPV genotypes (high-risk genotypes HPV16 and HPV18).</p><p><strong>Methods: </strong>We retrospectively analyzed blood samples at baseline prior to treatment from 92 patients diagnosed with HPV16- or HPV18-associated cervical cancer (FIGO IA2-IIIC2) between 2013 and 2020. HPV ctDNA was evaluated using digital droplet PCR.</p><p><strong>Results: </strong>HPV ctDNA was detected at baseline in 41.3% of cases. Locally advanced cervical cancers had a higher (p = 0.028) detection rate at baseline than early stage cervical cancers. HPV ctDNA positivity was significantly (p = 0.048) higher for HPV18 (60%) than for HPV16 (34.3%). Adenocarcinoma/adenosquamous carcinoma had a higher HPV ctDNA detection rate at baseline (54.2%) than squamous cell carcinoma (36.8%) but not significantly (p = 0.212) higher.</p><p><strong>Conclusion: </strong>This study found the impact of histology and HPV genotype on HPV ctDNA at baseline in cervical cancer. HPV18 and adenocarcinoma were associated with a higher baseline HPV ctDNA detection rate. These results suggest the need for different HPV ctDNA approaches for analyzing tumor burden. This finding may also serve as a useful reference for posttreatment surveillance studies.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-10"},"PeriodicalIF":3.5,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740052","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}
引用次数: 0
Validation of a Urine-Based Proteomics Test to Predict Clinically Significant Prostate Cancer: Complementing mpMRI Pathway. 验证基于尿液的蛋白质组学检验,预测具有临床意义的前列腺癌:补充 mpMRI 途径。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-11-11 DOI: 10.1159/000542465
Maria Frantzi, Ana C Morillo, Guillermo Lendinez, Ana Blanca, Daniel Lopez Ruiz, Jose Parada, Isabel Heidegger, Zoran Culig, Emmanouil Mavrogeorgis, Antonio Lopez Beltran, Marina Mora-Ortiz, Julia Carrasco-Valiente, Harald Mischak, Rafael A Medina, Pablo Campos Hernandez, Enrique Gómez Gómez
{"title":"Validation of a Urine-Based Proteomics Test to Predict Clinically Significant Prostate Cancer: Complementing mpMRI Pathway.","authors":"Maria Frantzi, Ana C Morillo, Guillermo Lendinez, Ana Blanca, Daniel Lopez Ruiz, Jose Parada, Isabel Heidegger, Zoran Culig, Emmanouil Mavrogeorgis, Antonio Lopez Beltran, Marina Mora-Ortiz, Julia Carrasco-Valiente, Harald Mischak, Rafael A Medina, Pablo Campos Hernandez, Enrique Gómez Gómez","doi":"10.1159/000542465","DOIUrl":"10.1159/000542465","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer (PCa) is the most frequently diagnosed cancer among men. A major clinical need is to accurately predict clinically significant PCa (csPCa). A proteomics-based 19-biomarker model (19-BM) was previously developed using capillary electrophoresis-mass spectrometry (CE-MS) and validated in close to 1,000 patients at risk for PCa. This study aimed to validate 19-BM in a multicenter prospective cohort of 101 biopsy-naive patients using current diagnostic pathways.</p><p><strong>Methods: </strong>Urine samples from 101 patients with suspicious of PCa were analyzed using CE-MS. All patients underwent multiparametric or magnetic resonance imaging (mpMRI) using a 3-T system. The 19-BM score was estimated using support vector machine-based software (MosaCluster v1.7.0), employing the previously published cut-off criterion of -0.07. Diagnostic nomograms were investigated along with mpMRI.</p><p><strong>Results: </strong>Independent validation of 19-BM yielded a sensitivity of 77% and a specificity of 85% (AUC:0.81). This performance surpassed those of prostate-specific antigen (PSA; AUC:0.56) and PSA density (AUC:0.69). For PI-RADS≤ 3 patients, 19-BM showed a sensitivity of 86% and a specificity of 88%. Integrating 19-BM with mpMRI resulted in significantly better accuracy (AUC:0.90) compared to individual investigations alone (AUC19BM = 0.81; p = 0.004 and AUCmpMRI: 0.79; p = 0.001). Examining the decision curve analysis, 19-BM with mpMRI surpassed other approaches for the prevailing risk interval from a 30% cut-off.</p><p><strong>Conclusions: </strong>19-BM exhibited favorable reproducibility for the prediction of csPCa. In patients with PI-RADS ≤3, 19-BM correctly classified 88% of the patients with insignificant PCa at the cost of 1 missed csPCa patient. Utilizing the 19-BM test could prove valuable in complementing mpMRI and reducing the need for unnecessary biopsies.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-10"},"PeriodicalIF":3.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625468","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}
引用次数: 0
Nodal T-Cell Lymphoma Transdifferentiated from Mantle Cell Lymphoma with Epstein-Barr Virus Infection. 从套细胞淋巴瘤转移而来的结节性T细胞淋巴瘤,伴有Epstein-Barr病毒感染。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-10-15 DOI: 10.1159/000541974
Paul D Barone, Wayne Tam, Julia T Geyer, John P Leonard, Adrienne Phillips, Madhu M Ouseph
{"title":"Nodal T-Cell Lymphoma Transdifferentiated from Mantle Cell Lymphoma with Epstein-Barr Virus Infection.","authors":"Paul D Barone, Wayne Tam, Julia T Geyer, John P Leonard, Adrienne Phillips, Madhu M Ouseph","doi":"10.1159/000541974","DOIUrl":"10.1159/000541974","url":null,"abstract":"<p><strong>Introduction: </strong>We report a case of mantle cell lymphoma (MCL) with an apparent lineage switch to an EBV-positive T-cell lymphoma. Although lineage switch is a well-documented phenomenon in some hematolymphoid diseases, such as acute leukemias or histiocytic/dendritic cell neoplasms, lineage switch from mature B-cell to T-cell lymphoma is exceedingly rare.</p><p><strong>Case presentation: </strong>A 55-year-old man with an established history of MCL presented to our institution. Peripheral blood flow cytometry was consistent with MCL. Biopsy of a lumbar vertebral fracture site demonstrated MCL, EBV-associated, with large cells reminiscent of high-grade transformation (BCL1-positive). Two months later, a lymph node biopsy demonstrated an EBV-positive T-cell lymphoma without phenotypic evidence of B-cell lymphoma (BCL1-negative). Cytogenetic testing revealed CCND1::IGH fusion in all three specimens. IGH/IGK clonality testing revealed conserved monoclonal peaks in all three samples; TCR clonality testing revealed monoclonal peaks in the T-cell lymphoma, only. NGS-based molecular genetic studies revealed shared mutations between the three samples, consistent with a clonal relationship suggesting evolution from MCL to T-cell lymphoma.</p><p><strong>Conclusions: </strong>This case demonstrates that lineage switch from mature B-cell to mature T-cell phenotype is possible in certain settings. Whether lineage switch in this case was potentiated by EBV infection is unclear. The loss of BCL1 expression in the T-cell lymphoma, despite conservation of the CCND1::IGH fusion, may be attributable to the downregulation of the IGH promoter as part of the shift from B-cell to T-cell phenotype.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-12"},"PeriodicalIF":3.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471983","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}
引用次数: 0
Human Papilloma Virus-Related Oral Mucosal Lesions in Turkey: A Retrospective Cohort Study. 火鸡人乳头状瘤病毒相关口腔黏膜病变:一项回顾性队列研究。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-10-09 DOI: 10.1159/000541664
Leyla Arslan Bozdag, Sibel Elif Gultekin
{"title":"Human Papilloma Virus-Related Oral Mucosal Lesions in Turkey: A Retrospective Cohort Study.","authors":"Leyla Arslan Bozdag, Sibel Elif Gultekin","doi":"10.1159/000541664","DOIUrl":"10.1159/000541664","url":null,"abstract":"<p><strong>Introduction: </strong>The human papillomavirus (HPV) is the etiological agent of a variety of oral mucosal benign and pre/malignant lesions, which demonstrate a wide range of prevalence according to geographic regions.</p><p><strong>Material and methods: </strong>This study specifically examined the typing of HPV-associated oral mucosal lesions in Turkish patients. The DNA from FFPE blocks of 228 lesions was utilized for this purpose. A total of 87 oral mucosal lesions were classified as benign, 68 as premalignant, and 73 as malignant. DNA from these lesions was amplified using polymerase chain reaction, and genotypes were identified using restriction fragment length polymorphisms (RFLP).</p><p><strong>Results: </strong>HPV-DNA was identified in 17 out of 228 patients, indicating a prevalence incidence of 7.4%. In benign oral lesions, the prevalence of HPV-DNA was 9.2% (8/87 cases), whereas in premalignant, oral epithelial dysplasia, and oral squamous cell carcinoma lesions, it was 6.9% (9/141 cases). A significant statistical difference was found between patients who tested positive for HPV and those who tested negative in terms of the location of the lesion and the age of the patients (p = 0.0097, p = 0.02, respectively).</p><p><strong>Conclusions: </strong>This study underscores the considerable prevalence of HPV infection in oral mucosal lesions among individuals in Central Anatolia, Turkey.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-9"},"PeriodicalIF":3.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392282","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}
引用次数: 0
Next-Generation Integrated Sequencing Identifies Poor Prognostic Factors in Patients with MYD88-Mutated Chronic Lymphocytic Leukemia in Taiwan. 下一代综合测序发现台湾MYD88突变慢性淋巴细胞白血病患者的不良预后因素。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-10-02 DOI: 10.1159/000541709
Ying-Jung Huang, Jing Quan Lim, Jacob Shujui Hsu, Ming-Chung Kuo, Po-Nan Wang, Hsiao-Wen Kao, Jin-Hou Wu, Chiu-Chen Chen, Shih-Feng Tsai, Choon Kiat Ong, Lee-Yung Shih
{"title":"Next-Generation Integrated Sequencing Identifies Poor Prognostic Factors in Patients with MYD88-Mutated Chronic Lymphocytic Leukemia in Taiwan.","authors":"Ying-Jung Huang, Jing Quan Lim, Jacob Shujui Hsu, Ming-Chung Kuo, Po-Nan Wang, Hsiao-Wen Kao, Jin-Hou Wu, Chiu-Chen Chen, Shih-Feng Tsai, Choon Kiat Ong, Lee-Yung Shih","doi":"10.1159/000541709","DOIUrl":"10.1159/000541709","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western countries and is very rare in Asia.</p><p><strong>Methods: </strong>Peripheral blood or bone marrow mononuclear cells obtained at initial diagnosis from 215 patients with CLL were analyzed by using next-generation sequencing to investigate the ethnic differences in genetic abnormalities.</p><p><strong>Results: </strong>Whole-genome sequencing and whole-exome sequencing analyses on 30 cases showed that 9 genes, including IGLL5, MYD88, TCHH, DSCAM, AXDND1, BICRA, KMT2D, MYT1L, and RBM43, were more frequently mutated in our Taiwanese cohort compared with those of the Western cohorts. IGLL5, MYD88, and KMT2D genes were further analyzed by targeted sequencing in another 185 CLL patients, unraveling frequencies of 29.3%, 20.9%, and 15.0%, respectively. The most frequent positional mutation of MYD88 was V217F (26/45, 57.8%), followed by L265P (9/45, 20.0%). MYD88 mutations were significantly associated with IGLL5 mutations (p = 0.0004), mutated IGHV (p < 0.0001) and 13q deletion (p = 0.0164). CLL patients with co-occurrence of MYD88 mutations with KMT2D or/and IGLL5 mutations were associated with a significantly inferior survival compared to those with MYD88 mutation alone (not reached vs. 131.8 months, p = 0.007). In multivariate analysis, MYD88 mutation without KMT2D or IGLL5 mutations was an independently favorable predictor.</p><p><strong>Conclusions: </strong>IGLL5, MYD88, and KMT2D mutations were enriched in Taiwanese CLL, and co-occurrence of MYD88 mutations with KMT2D or/and IGLL5 mutations was associated with a poorer prognosis.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-13"},"PeriodicalIF":3.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366117","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}
引用次数: 0
p16 Immunohistochemical Patterns in Triple-Negative Breast Cancer: Clinical and Genomic Similarities of the p16 Diffuse Pattern to pRB Deficiency. 三阴性乳腺癌的 p16 免疫组化模式:p16 扩散模式与 pRB 缺陷的临床和基因组相似性。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-09-06 DOI: 10.1159/000541299
Miseon Lee, Ahwon Lee, Byung-Ock Choi, Woo-Chan Park, Jieun Lee, Jun Kang
{"title":"p16 Immunohistochemical Patterns in Triple-Negative Breast Cancer: Clinical and Genomic Similarities of the p16 Diffuse Pattern to pRB Deficiency.","authors":"Miseon Lee, Ahwon Lee, Byung-Ock Choi, Woo-Chan Park, Jieun Lee, Jun Kang","doi":"10.1159/000541299","DOIUrl":"10.1159/000541299","url":null,"abstract":"<p><strong>Introduction: </strong>Triple-negative breast cancer (TNBC) is associated with alterations in the retinoblastoma pathway. As a consequence of retinoblastoma protein (pRB) loss, compensatory upregulation of p16 occurs due to the loss of phosphorylated pRB-mediated negative feedback on p16 expression. The aim of this study is to investigate the clinicopathological and genomic characteristics associated with the diffuse pattern of p16 immunohistochemistry (IHC) in TNBC.</p><p><strong>Methods: </strong>The study analyzed surgically resected TNBC for whole-exome sequencing in 113 cases and for cDNA microarray in 144 cases. The p16 IHC results were classified into two patterns: diffuse and negative/mosaic.</p><p><strong>Results: </strong>In the entire cohort (n = 257), the diffuse pattern of p16 IHC was observed in 123 (47.9%) patients and the negative/mosaic pattern in 134 (52.1%). Biallelic RB1 inactivation was observed in 14.3% of patients with the diffuse pattern. The diffuse pattern of p16 IHC showed more frequent RB1 alterations and cell cycle progression signatures, a higher Ki-67 labeling index, more frequent chromosome segment copy number changes, a higher frequency of homologous recombination deficiency high, and immune-related signatures. PIK3CA mutations were more frequent in the negative/mosaic pattern. CCND1 amplification was identified in 5 cases, all with the negative/mosaic pattern.</p><p><strong>Conclusion: </strong>In TNBC, the diffuse p16 pattern shows clinical and genomic similarities to pRB-deficient tumors, suggesting shared characteristics. This suggests that p16 IHC testing may provide new therapeutic approaches, underscoring its potential clinical importance.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-14"},"PeriodicalIF":3.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154771","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}
引用次数: 0
Artificial Intelligence Recognition Model Using Liquid-Based Cytology Images to Discriminate Malignancy and Histological Types of Non-Small-Cell Lung Cancer. 利用液基细胞学图像区分非小细胞肺癌恶性程度和组织学类型的人工智能识别模型
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-08-28 DOI: 10.1159/000541148
Ryota Tanaka, Yukihiro Tsuboshita, Mitsuaki Okodo, Rei Settsu, Kohei Hashimoto, Keisei Tachibana, Kazumasa Tanabe, Koji Kishimoto, Masachika Fujiwara, Junji Shibahara
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