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Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis. VSNL1的过表达增强了结直肠癌发生过程中的细胞增殖。
IF 5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-10-05 DOI: 10.1159/000533877
Takayuki Aiba, Naoki Hijiya, Tomonori Akagi, Yoshiyuki Tsukamoto, Yuka Hirashita, Keisuke Kinoshita, Tomohisa Uchida, Chisato Nakada, Shusaku Kurogi, Yoshitake Ueda, Hidefumi Shiroshita, Norio Shiraishi, Kazunari Murakami, Masafumi Inomata, Masatsugu Moriyama
{"title":"Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis.","authors":"Takayuki Aiba, Naoki Hijiya, Tomonori Akagi, Yoshiyuki Tsukamoto, Yuka Hirashita, Keisuke Kinoshita, Tomohisa Uchida, Chisato Nakada, Shusaku Kurogi, Yoshitake Ueda, Hidefumi Shiroshita, Norio Shiraishi, Kazunari Murakami, Masafumi Inomata, Masatsugu Moriyama","doi":"10.1159/000533877","DOIUrl":"10.1159/000533877","url":null,"abstract":"<p><strong>Introduction: </strong>We have previously reported that overexpression of visinin-like protein 1 (VSNL1) is frequently observed in advanced colorectal adenocarcinomas and correlates with poorer prognosis. In this study, we determined the levels of VSNL1 expression in the earlier stages of colorectal tumors including adenomas and adenocarcinomas, and attempted to clarify the functional significance of VSNL1 overexpression in colorectal carcinogenesis.</p><p><strong>Methods: </strong>Levels of VSNL expression in colorectal tumor tissues were analyzed using immunohistochemistry. The effects of VSNL1 downregulation and overexpression on cell proliferation, resistance to apoptosis, and invasiveness were determined using two VSNL1-overexpressing colorectal cancer cell lines, CW-2 and HCT-116 and VSNL1 inducibly expressing SNU-C5, respectively. Gene expression signatures in VSNL1-downregulated CW-2 and HCT-116 were identified using transcriptome and gene set enrichment analyses.</p><p><strong>Results: </strong>VSNL1 expression was restricted to only a few crypt cells in the non-tumorous epithelium, whereas it became enhanced in adenomas and adenocarcinomas with the progression of tumorigenesis. Downregulation of VSNL1 in CW-2 and HCT-116 cells suppressed their proliferation through induction of apoptosis. Conversely, overexpression of VSNL1 in SNU-C5 cells enhanced resistance to anoikis. Transcriptome and gene set enrichment analyses revealed that downregulation of VSNL1 altered the expression level of the apoptosis-related gene set in CW-2 and HCT-116 cells.</p><p><strong>Conclusion: </strong>VSNL1 plays a role in both the development and progression of colorectal tumors by enhancing cell viability.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41145835","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
Morphologic Heterogeneity of Carcinoma with Signet Ring Cell Features at Different Primary Sites. 不同原发部位具有印戒细胞特征的癌的形态异质性。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-12-23 DOI: 10.1159/000535941
Wissam Dahoud, Irene Gullo, Rami Imam, Laura H Tang
{"title":"Morphologic Heterogeneity of Carcinoma with Signet Ring Cell Features at Different Primary Sites.","authors":"Wissam Dahoud, Irene Gullo, Rami Imam, Laura H Tang","doi":"10.1159/000535941","DOIUrl":"10.1159/000535941","url":null,"abstract":"<p><strong>Introduction: </strong>Signet ring cells (SRCs) may be observed in carcinomas from multiple primary sites. Elucidating unknown primaries from metastases with SRCs represents a diagnostic challenge. This study examined morphologic characteristics of adenocarcinomas with SRCs from stablished primary sites and described objective features, which can aid in identifying the site of origin.</p><p><strong>Methods: </strong>The series encompasses 257 cases of adenocarcinomas with SRCs from gastroesophageal junction (GEJ, n = 38), stomach (n = 48), pancreatobiliary system (n = 16), colorectum (n = 40), appendix (n = 32), breast (n = 41), and lung (n = 42). H&amp;E sections were examined and scored using architectural and cytologic criteria. Morphometric analysis was performed using QuPath software.</p><p><strong>Results: </strong>Extracellular mucin was more abundant in GEJ, colorectal, and appendiceal carcinomas. Poorly cohesive morphology was the most frequent pattern in gastric and breast carcinomas. The cytoplasmic mucin/vacuole was predominantly clear and targetoid in breast carcinomas. Breast and gastric carcinomas showed the highest nuclear to cytoplasmic (N/C) ratio, whereas appendiceal carcinoma the lowest.</p><p><strong>Conclusion: </strong>Morphological evaluation (extracellular mucin, architectural patterns, and the nature of cytoplasmic mucin/vacuole) represents an important step to determine the cancer site of origin in adenocarcinomas with SRCs and guides further ancillary studies. Cytological morphometry may help further refine morphological criteria and facilitate the construction of digital-pathology algorithms.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032511","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
Discrepancies in Hormone Receptor and HER2 Expression between Malignant Serous Effusions and Paired Tissues from Primary or Recurrent Breast Cancers. 原发性或复发性乳腺癌恶性浆液性渗出物和配对组织之间激素受体和HER2表达的差异。
IF 5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-10-10 DOI: 10.1159/000533912
Ilias P Nikas, Sojung Lim, Seock-Ah Im, Kyung-Hun Lee, Dae-Won Lee, Hyebin Lee, Han Suk Ryu
{"title":"Discrepancies in Hormone Receptor and HER2 Expression between Malignant Serous Effusions and Paired Tissues from Primary or Recurrent Breast Cancers.","authors":"Ilias P Nikas, Sojung Lim, Seock-Ah Im, Kyung-Hun Lee, Dae-Won Lee, Hyebin Lee, Han Suk Ryu","doi":"10.1159/000533912","DOIUrl":"10.1159/000533912","url":null,"abstract":"<p><strong>Introduction: </strong>Immunohistochemistry (IHC) for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) biomarkers has prognostic and therapeutic value in breast cancer. This study aimed to compare the expression of ER, PR, and HER2 between paired malignant effusions and tissue samples of breast cancer.</p><p><strong>Methods: </strong>Our electronic archive was searched for all effusions diagnosed as breast carcinomas within a pre-defined period (January 2018-October 2021). Next, their cell blocks (CBs) were subjected to ER, PR, HER2 IHC, or in situ hybridization, in addition to EGFR IHC. The expression of hormone receptors (HRs) and HER2 was subsequently compared between tissue and effusion cytology samples derived from the same patients.</p><p><strong>Results: </strong>Only 2/76 (2.6%) of the breast cancer patients analyzed showed a malignant effusion at their initial presentation. ER, PR, and HER2 discordance rates between paired malignant effusions and tissue samples obtained at initial diagnosis were 24.3% (17/73), 40.8% (29/71), and 9.1% (6/66), respectively. The HR-/HER2- status was found more often at effusions compared to paired tissue biopsies obtained at initial diagnosis (30/70 vs. 17/70; p &lt; 0.001). In addition, the HR-/HER2- status was significantly associated with an earlier development of a malignant effusion, when found at initial diagnosis (p &lt; 0.001; log-rank test), first recurrence/metastasis (either solid or effusion) (p = 0.012; log-rank test), effusion samples (p = 0.007; log-rank test), and any tumor sample obtained (p = 0.009; log-rank test). Lastly, EGFR overexpression in the HR-/HER2- effusion samples was significantly associated with a shorter post-effusion survival (p = 0.019; log-rank test).</p><p><strong>Conclusion: </strong>Serous effusion cytology provides high-quality material for ancillary techniques, especially when CBs are prepared, reflecting cancer heterogeneity.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41208322","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
Expression Profile of Microenvironmental Factors in the Interface Zone of Colorectal Cancer: Histological-Stromal Biomarkers and Cancer Cell-Cancer-Associated Fibroblast-Related Proteins Combined for the Assessment of Tumor Progression. 结直肠癌界面区微环境因素的表达谱:组织学-基质生物标记物与癌细胞-癌相关成纤维细胞相关蛋白相结合评估肿瘤进展。
IF 5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-06-27 DOI: 10.1159/000531695
Ricella Souza da Silva, Eduardo M Queiroga, Cynthia de Toledo Osório, Karin S Cunha, Fabiana P Neves, Julieth P Andrade, Eliane P Dias
{"title":"Expression Profile of Microenvironmental Factors in the Interface Zone of Colorectal Cancer: Histological-Stromal Biomarkers and Cancer Cell-Cancer-Associated Fibroblast-Related Proteins Combined for the Assessment of Tumor Progression.","authors":"Ricella Souza da Silva, Eduardo M Queiroga, Cynthia de Toledo Osório, Karin S Cunha, Fabiana P Neves, Julieth P Andrade, Eliane P Dias","doi":"10.1159/000531695","DOIUrl":"10.1159/000531695","url":null,"abstract":"<p><strong>Introduction: </strong>The characterization of tumor microenvironment (TME) related factors and their impact on tumor progression have attracted much interest. We investigated cancer cells and cancer-associated fibroblasts (CAFs) to evaluate biomarkers that are associated with neoplastic progression, observing them in different interface zones of colorectal cancer.</p><p><strong>Methods: </strong>On 357 CRC tissue microarrays, using immunohistochemistry, we examined the associations of podoplanin and α-SMA expressed in cancer cells and CAFs and evaluated them in different areas: tumor core, invasive front, tumor budding, tumor-stroma ratio (TSR) scoring, and desmoplastic stroma.</p><p><strong>Results: </strong>CAFs expressing α-SMA were found in more than 90% of the cases. Podoplanin+ was detected in cancer cells and CAFs, with positivities of 38.6% and 70%, respectively. Higher α-SMA+ CAFs and podoplanin+ cancer cells were observed predominantly at the TSR score area: 94.3% and 64.3% of cases, respectively. The status of podoplanin in CAFs+ was higher in the desmoplastic area (71.6%). Stroma-high tumors showed increased expression of α-SMA and podoplanin in comparison with stroma-low tumors. The status of podoplanin in cancer cells was observed in association with lymphatic invasion and distant metastasis.</p><p><strong>Conclusion: </strong>The substance of the CRC was composed predominantly of the surrounding stroma-α-SMA+ CAFs. Podoplanin expressed in the prognosticator zones was associated with unfavorable pathological features. The combination of histologic and protein-related biomarkers can result in a tool for the stratification of patients with CRC.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9695916","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
The Pathology according to p53 Pathway. 病理依据p53通路。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-11-14 DOI: 10.1159/000535203
Yuichiro Hatano
{"title":"The Pathology according to p53 Pathway.","authors":"Yuichiro Hatano","doi":"10.1159/000535203","DOIUrl":"10.1159/000535203","url":null,"abstract":"<p><strong>Background: </strong>Observations play a pivotal role in the progress of science, including in pathology. The cause of a disease such as cancer is analyzed by breaking it down into smaller organs, tissues, cells, and molecules. The current standard cancer diagnostic procedure, microscopic observation, relies on preserved morphological characteristics. In contrast, molecular analyses explore oncogenic pathway activation that leads to genetic mutations and aberrant protein expression. Such molecular analyses could potentially identify therapeutic targets and has gained considerable attention in clinical oncology.</p><p><strong>Summary: </strong>This review summarizes the cardinal biomarkers of the p53 pathway, p53, p16, and mouse double minute 2 (MDM2), in the context of traditional surgical pathology and emerging genomic oncology. The p53 pathway, which is dysregulated in more than a half of all cancers, can be applied in several diagnostic settings. A four-classification model of immunophenotype for p53 pathway gene status, tumor types with a high frequency of abnormalities for each p53 pathway gene, and a minimal p53 pathway immunohistochemical panel is also described.</p><p><strong>Key messages: </strong>Immunohistochemistry of oncogenic signals should be interpreted according to molecular findings based on genomic oncology, in addition to the microscopic findings of diagnostic pathology.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11313058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107591958","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}
引用次数: 0
Exploring the Expression of Adenosine Pathway-Related Markers CD73 and CD39 in Colorectal and Pancreatic Carcinomas Characterized by Multiplex Immunofluorescence: A Pilot Study. 探讨腺苷途径相关标记物CD73和CD39在以多重免疫荧光为特征的结直肠癌和胰腺癌中的表达:一项初步研究。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-11-03 DOI: 10.1159/000534677
Cibelle Freitas Lima, Auriole Tamegnon, Saxon Rodriguez, Dipen Maru, Philip L Martin, Zachary A Cooper, Jaime Rodriguez-Canales, Edwin Roger Parra
{"title":"Exploring the Expression of Adenosine Pathway-Related Markers CD73 and CD39 in Colorectal and Pancreatic Carcinomas Characterized by Multiplex Immunofluorescence: A Pilot Study.","authors":"Cibelle Freitas Lima, Auriole Tamegnon, Saxon Rodriguez, Dipen Maru, Philip L Martin, Zachary A Cooper, Jaime Rodriguez-Canales, Edwin Roger Parra","doi":"10.1159/000534677","DOIUrl":"10.1159/000534677","url":null,"abstract":"<p><strong>Introduction: </strong>Generating high levels of immunosuppressive adenosine (ADO) in the tumor microenvironment contributes to cancer immune evasion. CD39 and CD73 hydrolyze adenosine triphosphate into ADO; thus, efforts have been made to target this pathway for cancer immunotherapy. Our objective was optimizing a multiplex immunofluorescence (mIF) panel to explore the role of CD39 and CD73 within the tumor microenvironment.</p><p><strong>Materials and methods: </strong>In three-time points, a small cohort (n = 8) of colorectal and pancreatic adenocarcinomas were automated staining using an mIF panel against CK, CD3, CD8, CD20, CD39, CD73, and CD68 to compare them with individual markers immunohistochemistry (IHC) for internal panel validation. Densities of immune cells and distances from different tumor-associated immune cells to tumor cells were exploratory assessment and compared with clinicopathologic variables and outcomes.</p><p><strong>Results: </strong>Comparing the three-time points and individual IHC staining results, we demonstrated high reproducibility of the mIF panel. CD39 and CD73 expression was low in malignant cells; the exploratory analysis showed higher densities of CD39 expression by various cells, predominantly stromal cells, followed by T cells, macrophages, and B cells. No expression of CD73 by B cells or macrophages was detected. Distance analysis revealed proximity of cytotoxic T cells, macrophages, and T cells expressing CD39 to malignant cells, suggesting a close regulatory signal driven by this ADO marker.</p><p><strong>Conclusions: </strong>We optimized an mIF panel for detection of markers in the ADO pathway, an emerging clinically relevant pathway. The densities and spatial distribution demonstrated that this pathway may modulate aspects of the tumor immune microenvironment.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71484697","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}
引用次数: 0
Detection of Hybrid Fusion Transcripts, Aberrant Transcript Expression, and Specific Single Nucleotide Variants in Acute Leukemia and Myeloid Disorders with Recurrent Gene Rearrangements. 检测急性白血病和髓系疾病中的杂交融合转录本、异常转录本表达和特定单核苷酸变异与复发性基因重排。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-07-25 DOI: 10.1159/000532085
Yuewei Li, Kaifang Deng, Justin Kaner, Julia T Geyer, Madhu Ouseph, Frank Fang, Kemin Xu, Gail Roboz, Michael J Kluk
{"title":"Detection of Hybrid Fusion Transcripts, Aberrant Transcript Expression, and Specific Single Nucleotide Variants in Acute Leukemia and Myeloid Disorders with Recurrent Gene Rearrangements.","authors":"Yuewei Li, Kaifang Deng, Justin Kaner, Julia T Geyer, Madhu Ouseph, Frank Fang, Kemin Xu, Gail Roboz, Michael J Kluk","doi":"10.1159/000532085","DOIUrl":"10.1159/000532085","url":null,"abstract":"<p><strong>Introduction: </strong>A variety of gene rearrangements and molecular alterations are key drivers in the pathobiology of acute leukemia and myeloid disorders; current classification systems increasingly incorporate these findings in diagnostic algorithms. Therefore, clinical laboratories require versatile tools, which can detect an increasing number and variety of molecular and cytogenetic alterations of clinical significance.</p><p><strong>Methods: </strong>We validated an RNA-based next-generation sequencing (NGS) assay that enables the detection of: (i) numerous hybrid fusion transcripts (including rare/novel gene partners), (ii) aberrantly expressed EVI1 (MECOM) and IKZF1 (Del exons 4-7) transcripts, and (iii) hotspot variants in KIT, ABL1, NPM1 (relevant in the context of gene rearrangement status).</p><p><strong>Results: </strong>For hybrid fusion transcripts, the assay showed 98-100% concordance for known positive and negative samples, with an analytical sensitivity (i.e., limit of detection) of approximately 0.8% cells. Samples with underlying EVI1 (MECOM) translocations demonstrated increased EVI1 (MECOM) expression. Aberrant IKZF1 (Del exons 4-7) transcripts detectable with the assay were also present on orthogonal reverse transcription PCR. Specific hotspot mutations in KIT, ABL1, and NPM1 detected with the assay showed 100% concordance with orthogonal testing. Lastly, several illustrative samples are included to highlight the assay's clinically relevant contributions to patient workup.</p><p><strong>Conclusion: </strong>Through its ability to simultaneously detect various gene rearrangements, aberrantly expressed transcripts, and hotspot mutations, this RNA-based NGS assay is a valuable tool for clinical laboratories to supplement other molecular and cytogenetic methods used in the diagnostic workup and in clinical research for patients with acute leukemia and myeloid disorders.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9861442","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}
引用次数: 0
Differential Gene Expression of SARS-CoV-2 Positive Bronchoalveolar Lavages: A Case Series. SARS-CoV-2 阳性支气管肺泡灌洗液的不同基因表达:病例系列。
IF 5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-07-25 DOI: 10.1159/000532057
Jasmin D Haslbauer, Spasenija Savic Prince, Anna K Stalder, Matthias S Matter, Carl P Zinner, Kathleen Jahn, Ellen Obermann, Jasmin Hanke, Karoline Leuzinger, Hans H Hirsch, Alexandar Tzankov
{"title":"Differential Gene Expression of SARS-CoV-2 Positive Bronchoalveolar Lavages: A Case Series.","authors":"Jasmin D Haslbauer, Spasenija Savic Prince, Anna K Stalder, Matthias S Matter, Carl P Zinner, Kathleen Jahn, Ellen Obermann, Jasmin Hanke, Karoline Leuzinger, Hans H Hirsch, Alexandar Tzankov","doi":"10.1159/000532057","DOIUrl":"10.1159/000532057","url":null,"abstract":"<p><strong>Background: </strong>Transcriptomic data on bronchoalveolar lavage (BAL) from COVID-19 patients are currently scarce.</p><p><strong>Objectives: </strong>This case series seeks to characterize the intra-alveolar immunopathology of COVID-19.</p><p><strong>Method: </strong>BALs were performed on 14 patients (5 COVID-19, of which 3 mild and 2 largely asymptomatic, 9 controls). Controls included asthma (n = 1), unremarkable BALs (n = 3), infections with respiratory syncytial virus (n = 1), influenza B (n = 1), and infections with other coronaviruses (n = 3). SARS-CoV-2 RNA load was measured by quantitative nucleic acid testing, while the detection of other pathogens was performed by immunofluorescence or multiplex NAT.</p><p><strong>Results: </strong>Gene expression profiling showed 71 significantly downregulated and 5 upregulated transcripts in SARS-CoV-2-positive lavages versus controls. Downregulated transcripts included genes involved in macrophage development, polarization, and crosstalk (LGALS3, MARCO, ERG2, BTK, RAC1, CD83), and genes involved in chemokine signaling and immunometabolism (NUPR1, CEBPB, CEBPA, PECAM1, CCL18, PPARG, ALOX5, ALOX5AP). Upregulated transcripts featured genes involved in NK-T cell signaling (GZMA, GZMH, GNLY, PRF1, CD3G). Patients with mild COVID-19 showed a significant upregulation of genes involved in blood mononuclear cell/leukocyte function (G0S2, ANXA6, FCGR2B, ADORA3), coagulation (von Willebrand factor [VWF]), interferon response (IFRD1, IL12RB2), and a zinc metalloprotease elevated in asthma (CPA3) compared to asymptomatic cases. In-silico comparison of the 5 COVID-19 BAL cases to a published cohort of lethal COVID-19 showed a significant upregulation of \"antigen processing and presentation\" and \"lysosome\" pathways in lethal cases.</p><p><strong>Conclusions: </strong>These data underscore the heterogeneity of immune response in COVID-19. Further studies with a larger dataset are required to gain a better understanding of the hallmarks of SARS-CoV-2 immunological response.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9861443","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}
引用次数: 0
Prognostic Significance of Intratumoral and Peritumoral Budding in Distal Extrahepatic Bile Duct Carcinoma. 远端肝外胆管癌瘤内和瘤周萌发的预后意义
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-12-19 DOI: 10.1159/000535847
Sun-Young Jun, Seung-Mo Hong, Soyeon An
{"title":"Prognostic Significance of Intratumoral and Peritumoral Budding in Distal Extrahepatic Bile Duct Carcinoma.","authors":"Sun-Young Jun, Seung-Mo Hong, Soyeon An","doi":"10.1159/000535847","DOIUrl":"10.1159/000535847","url":null,"abstract":"<p><strong>Introduction: </strong>Although tumor budding (TB) has been recognized as a representative adverse prognosticator in gastrointestinal malignancies, it is not well elucidated in distal extrahepatic bile duct carcinoma (DBDC). Herein, we investigated the prognostic significance of peritumoral (PTB) and intratumoral (ITB) budding according to the modified DBDC staging of the 8th edition of the American Joint Committee on Cancer.</p><p><strong>Methods: </strong>PTB and ITB were independently evaluated in a cohort of DBDC patients (n = 410) based on the 2016 International Tumor Budding Consensus Conference.</p><p><strong>Results: </strong>High levels of PTB (PTBHigh, ≥ grade-2) and ITB (ITBHigh, ≥ grade-3) were identified in 316 (77%) and 238 (58%) cases, respectively. In univariate analysis, PTBHigh and ITBHigh, larger size and sclerosing tumor growth pattern, higher histologic grade, extrapancreatic location, adenocarcinomas unrelated to intraductal papillary neoplasm of the bile duct, pancreatic, duodenal, and lymphovascular invasion, perineural invasion, cancer involvement of the bile duct resection margin, nodal metastasis, and higher T and N categories and disease stages were associated with shorter patient overall survival (OS) times. In multivariate analysis, PTBHigh and ITBHigh remained poor independent prognostic indicators of OS in DBDC patients. Specifically, ITBHigh could predict poor prognosis in patients with stage I (T1N0) DBDC.</p><p><strong>Conclusions: </strong>Both PTBHigh and ITBHigh were strong prognostic indicators in patients with DBDC. Thus, ITB could be used to predict worse prognoses in patients with DBDC, in which PTB is difficult to assess, especially for patients with stage I (T1N0) DBDC.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801126","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}
引用次数: 0
Cytomorphological Disparities in Invasive Breast Cancer Cells following Neoadjuvant Endocrine Therapy and Chemotherapy. 新辅助内分泌治疗和化疗后浸润性乳腺癌细胞的细胞形态差异。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2024-03-12 DOI: 10.1159/000538227
Hideko Hoshina, Takashi Sakatani, Yoko Kawamoto, Ryuji Ohashi, Hiroyuki Takei
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