Pathobiology : journal of immunopathology, molecular and cellular biology最新文献

{"title":"Ex vivo Fusion Confocal Microscopy of Colorectal Polyps: A Fast Turnaround Time of Pathological Diagnosis.","authors":"Jose Andres Guerrero,&nbsp;Javiera Pérez-Anker,&nbsp;Gloria Fernández-Esparrach,&nbsp;Ivan Archilla,&nbsp;Alba Diaz,&nbsp;Sandra Lopez-Prades,&nbsp;Maite Rodrigo-Calvo,&nbsp;Sara Lahoz,&nbsp;Jordi Camps,&nbsp;Susana Puig,&nbsp;Josep Malvehy,&nbsp;Miriam Cuatrecasas","doi":"10.1159/000517190","DOIUrl":"https://doi.org/10.1159/000517190","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer screening programs have accomplished a mortality reduction from the disease but have created bottlenecks in endoscopy units and pathology departments. We aimed to explore the feasibility of ex vivo fusion confocal microscopy (FuCM) to improve the histopathology diagnostic efficiency and reduce laboratory workload.</p><p><strong>Methods: </strong>Consecutive fresh polyps removed at colonoscopy were scanned using ex vivo FuCM, then went through histopathologic workout and hematoxylin and eosin (H&amp;E) diagnosis. Two pathologists blinded to H&amp;E diagnosis made a diagnosis based on FuCM scanned images.</p><p><strong>Results: </strong>Thirty-six fresh polyps from 22 patients were diagnosed with FuCM and H&amp;E. Diagnostic agreement between H&amp;E and FuCM was 97.2% (kappa = 0.96) for pathologist #1 and 91.7% (kappa = 0.87) for pathologist #2. Diagnostic performance concordance between FuCM and H&amp;E to discern adenomatous from nonadenomatous polyps was 100% (kappa = 1) for pathologist #1 and 97.2% (kappa = 0.94) for pathologist #2. Global interobserver agreement was 94.44% (kappa = 0.91) and kappa = 0.94 to distinguish adenomatous from nonadenomatous polyps.</p><p><strong>Conclusions: </strong>Ex vivo FuCM shows an excellent correlation with standard H&amp;E for the diagnosis of colorectal polyps. The clinical direct benefit for patients, pathologists, and endoscopists allows adapting personalized surveillance protocols after colonoscopy and a workload decrease in pathology departments.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"392-399"},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39322722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long Non-Coding RNA ARAP1-AS1 Facilitates the Progression of Cervical Cancer by Regulating miR-149-3p and POU2F2.","authors":"Ling Zhou,&nbsp;Xiao-Li Xu","doi":"10.1159/000507830","DOIUrl":"https://doi.org/10.1159/000507830","url":null,"abstract":"<p><strong>Background: </strong>Emerging research has demonstrated that long non-coding RNAs (lncRNAs) attach great importance to the progression of cervical cancer (CC). LncRNA ARAP1-AS1 was involved in the development of several cancers; however, its role in CC is far from being elucidated.</p><p><strong>Methods: </strong>Real-time PCR (RT-PCR) was employed to detect ARAP1-AS1 and miR-149-3p expression in CC samples. CC cell lines (HeLa and C33A cells) were regarded as the cell models. The biological effect of ARAP1-AS1 on cancer cells was measured using CCK-8 assay, colony formation assay, flow cytometry, Transwell assay and wound healing assay in vitro, and subcutaneous xenotransplanted tumor model and tail vein injection model in vivo. Furthermore, interactions between ARAP1-AS1 and miR-149-3p, miR-149-3p and POU class 2 homeobox 2 (POU2F2) were determined by bioinformatics analysis, qRT-PCR, Western blot, luciferase reporter and RNA immunoprecipitation assay, respectively.</p><p><strong>Results: </strong>The expression of ARAP1-AS1 was enhanced in CC samples, while miR-149-3p was markedly suppressed. Additionally, ARAP1-AS1 overexpression enhanced the viability, migration, and invasion of CC cells. ARAP1-AS1 downregulated miR-149-3p via sponging it. ARAP1-AS1 and miR-149-3p exhibited a negative correlation in CC samples. On the other hand, ARAP1-AS1 enhanced the expression of POU2F2, which was validated as a target gene of miR-149-3p.</p><p><strong>Conclusion: </strong>ARAP1-AS1 was abnormally upregulated in CC tissues and indirectly modulated the POU2F2 expression via reducing miR-149-3p expression. Our study identified a novel axis, ARAP1-AS1/miR-149-3p/POU2F2, in CC tumorigenesis.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"301-312"},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000507830","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38963460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LRP1B Expression as a Putative Predictor of Response to Pegylated Liposomal Doxorubicin Treatment in Ovarian Cancer.","authors":"Isabel J Dionísio de Sousa,&nbsp;Ana Isabel Cunha,&nbsp;Inês A Saraiva,&nbsp;Raquel V Portugal,&nbsp;Etel R P Gimba,&nbsp;Marcos Guimarães,&nbsp;Hugo Prazeres,&nbsp;José M Lopes,&nbsp;Paula Soares,&nbsp;Raquel T Lima","doi":"10.1159/000517372","DOIUrl":"https://doi.org/10.1159/000517372","url":null,"abstract":"Background: Pegylated liposomal doxorubicin (PLD) is among the most active therapies for recurrent/progressive ovarian cancer (OC). Low-density lipoprotein receptor-related protein 1B (LRP1B) is one of the 10 most significantly deleted genes in human cancers. It mediates endocytosis of several factors from the cellular environment including liposomes. Although the LRP1B role in cancer has not been fully disclosed, its contribution to resistance to liposomal therapies has been hypothesized. This study aimed to evaluate the impact of LRP1B protein as a possible marker of response to PLD in patients with OC. Methods: LRP1B expression and response to PLD were analyzed in OC cell lines by qRT-PCR and PrestoBlue viability assay, respectively. LRP1B protein expression was evaluated for the first time, in tumor samples from PLD-treated patients and controls (other chemotherapies) by immunohistochemistry. Association of LRP1B staining score (determined based on intensity and percentage of positively stained cells) with clinicopathological features, response to therapy and survival outcomes was evaluated. Results: OC cells with increased expression of LRP1B were more sensitive to PLD. LRP1B staining score was associated with clinicopathological features, response to therapy, and survival outcomes. Higher LRP1B levels were associated with prolonged progression-free survival. This association was more evident in patients treated with PLD and in responders to PLD. Conclusion: Our results support a possible role of LRP1B as a predictor of response to PLD in patients with OC.","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"400-411"},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39553438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unusual Mesenchymal Tumors of the Lower Gastrointestinal Tract: When You Hear Hoofbeats in the Night, Do Not Forget the Zebras.","authors":"Marco Barella,&nbsp;Gianluca Lopez,&nbsp;Stefano Ferrero,&nbsp;Maurizio Vecchi,&nbsp;Paolo Cantù,&nbsp;Giorgio Alberto Croci,&nbsp;Francesca Boggio,&nbsp;Alessandro Del Gobbo","doi":"10.1159/000517962","DOIUrl":"https://doi.org/10.1159/000517962","url":null,"abstract":"<p><strong>Introduction: </strong>Little information about clinical presentation of mesenchymal tumors of the lower gastrointestinal (GI) tract due to their extreme heterogeneity is available for clinical management. Usually, small solitary asymptomatic polyps are accidently found during a screening colonoscopy performed for hematochezia, abdominal pain, constipation, diarrhea, and bowel obstruction. In this case series, we illustrate our experience with mesenchymal tumors of the lower GI tract, which are a group of unusual and quite challenging lesions.</p><p><strong>Case presentation: </strong>We retrospectively collected mesenchymal tumors of the lower GI tract in our institution (Fondazione IRCSS Ca' Granda - Ospedale Maggiore Policlinico di Milano) during the last 10 years. We reviewed the histological slides, and, when necessary, we performed immunohistochemical analyses to better characterize the tumors. A total of 99 cases were identified: 45 GISTs, 42 lipomas, 4 leiomyomas, 3 Kaposi sarcomas, 1 schwannoma, 1 ganglioneuroma, 1 hemangioma, 1 inflammatory fibroid polyp, and 1 challenging case of spindle cell melanoma. We focused on the most rare entities excluding therefore all GISTs and lipomas from re-evaluation.</p><p><strong>Conclusion: </strong>Mesenchymal tumors of the lower GI tract represent a highly heterogeneous group of lesions encompassing GISTs, lipomas, smooth muscle tumors (leiomyoma and leiomyosarcoma), GI schwannomas, inflammatory fibroid polyps, solitary fibrous tumors, and other unusual spindle cell tumors. Immunohistochemistry and, in selected cases, molecular biology remain a useful tool which, in addition to a meticulous study of the morphology, helps the pathologist in the tangled jungle of differential diagnosis.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"434-442"},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39740773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological and Molecular Study of Hybrid Oncocytic/Chromophobe Tumor of the Kidney Associated with Sporadic Renal Oncocytosis and Chronic B-Cell Lymphocytic Leukemia: The Possible Contribution of Lymphoma to Renal Oncocytosis.","authors":"Miguel A Idoate,&nbsp;Inmaculada Trigo,&nbsp;Jesús Saenz de Zaitigui,&nbsp;Manuel Pérez-Pérez,&nbsp;Juan José Ríos","doi":"10.1159/000515215","DOIUrl":"https://doi.org/10.1159/000515215","url":null,"abstract":"<p><p>Hybrid oncocytic/chromophobe tumor (HOCT) of the kidney arising from a precursor oncocytosis not associated with the Birt-Hogg-Dubé (BHD) syndrome is an unusual and highly interesting neoplasm. Immunohistochemical and molecular findings suggest that HOCT is an entity distinct from both oncocytoma and chromophobe carcinoma. Although uncertainty persists regarding the factors predisposing to the development of HOCT, experimental findings suggest that it may arise due to the effect of toxins or in association with chronic kidney failure. The potential role of prior renal lymphoma in the development of oncocytosis has not hitherto been examined. We present a morphological, immunohistochemical, and molecular analysis of an HOCT arising from renal oncocytosis in conjunction with CLL affecting the kidney. The findings suggest that this tumor belongs to a family of similar neoplasms including oncocytoma, the eosinophilic variant of chromophobe renal-cell carcinoma (CRCC), and low-grade oncocytic tumor, even though these neoplasms may arise from different precursor lesions. HOCT and oncocytosis revealed the same immunohistochemical profile consistent on positivity for epithelial membrane antigen (EMA), cytokeratin 7 (Ck7), E-cadherin, CAM 5.2 and negativity for Pax-8, vimentin, renal-cell carcinoma (RCC) antigen, CD117, racemase, progesterone receptor, and CD10. The Ki-67 proliferation index was <1%. Molecular analysis of the tumor revealed the AKT3 gene mutation variant, classified as probably pathogenic, together with FOS1 gene amplification and no copy number variations (CNVs). Finally, we present a case of HOCT arising from a nonhereditary renal oncocytosis in conjunction with B lymphoma that raises interesting questions regarding pathogenesis.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"313-322"},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000515215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38895161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Glucose Metabolism-Related Proteins in Adrenal Neoplasms.","authors":"Eun Kyung Kim,&nbsp;Hye Min Kim,&nbsp;Ja Seung Koo","doi":"10.1159/000518208","DOIUrl":"https://doi.org/10.1159/000518208","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to investigate the expression patterns of glucose metabolism-related proteins and their clinicopathologic implications in adrenal cortical neoplasms (ACN) and pheochromocytoma (PCC).</p><p><strong>Methods: </strong>Immunohistochemical staining was performed to evaluate glucose metabolism-related proteins (GLUT1, CAIX, hexokinase II, G6PDH, PHGDH, and SHMT1) in 132 ACN cases (115 adrenal cortical adenoma [ACA] and 17 adrenal cortical carcinoma [ACC]) and 189 PCC cases.</p><p><strong>Results: </strong>Expression levels of GLUT1 in tumor cells ([T]; p < 0.001), GLUT1 in stromal cells ([S]; p < 0.001), G6PDH (p < 0.001), and SHMT1 (p = 0.002) were higher in ACN than in PCC. GLUT1 (T; p = 0.045) and PHGDH (p = 0.043) levels were higher in ACC than in ACA. In a univariate analysis of ACN, GLUT1 (T; p = 0.017), CAIX (S; p = 0.003), and PHGDH (p = 0.009) levels were correlated with a shorter overall survival (OS). GLUT1 (T; p = 0.001) and PHGDH (p < 0.001) were related to a shorter OS in PCC. GLUT1 (T) positivity (p = 0.043) in ACN predicted a poor OS in a multivariate Cox analysis. In PCC, high GAPP score (p = 0.026), GLUT1 (T; p = 0.002), and PHGDH (p < 0.001) were independent prognostic factors for poor OS.</p><p><strong>Conclusions: </strong>The adrenal gland tumors ACN and PCC had different expression patterns of glucose metabolism-related proteins (GLUT1, G6PDH, and SHMT1), with higher expression levels in ACN than in PCC. GLUT1 and PHGDH were significant prognostic factors in these adrenal neoplasms.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"424-433"},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39413633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long Noncoding RNA GAS5 Targeting miR-221-3p/Cyclin-Dependent Kinase Inhibitor 2B Axis Regulates Follicular Thyroid Carcinoma Cell Cycle and Proliferation.","authors":"Yuan Liu,&nbsp;Yi-Fang Li,&nbsp;Jia Liu,&nbsp;Zhi-Gang Deng,&nbsp;Li Zeng,&nbsp;Wei-Bing Zhou","doi":"10.1159/000513338","DOIUrl":"https://doi.org/10.1159/000513338","url":null,"abstract":"<p><strong>Introduction: </strong>Follicular thyroid carcinoma (FTC) is more aggressive than the most common papillary thyroid carcinoma (PTC). However, the current research on FTC is less than PTC. Here, we investigated the effects of long noncoding RNA (lncRNA) GAS5 and miR-221-3p in FTC.</p><p><strong>Methods: </strong>Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect GAS5 and miR-221-3p expression in the FTC tissues and cells. Cell proliferation was assessed by CCK8 and EdU assays. Flow cytometry was performed to determine the cell cycle. The dual-luciferase reporter assay was employed to validate the binding relationship of GAS5/miR-221-3p and miR-221-3p/cyclin-dependent kinase inhibitor 2B (CDKN2B). Western blot was conducted to measure the protein level of CDKN2B.</p><p><strong>Results: </strong>Our results displayed that GAS5 was downregulated, while miR-221-3p was upregulated in FTC tissues and cells. What's more, overexpression of GAS5 or miR-221-3p inhibition induced G0/G1 phase arrest and inhibited cell proliferation of FTC cells. GAS5 acted as a sponge of miR-221-3p, and CDKN2B was a target gene of miR-221-3p. Additionally, GAS5 inhibited cell cycle and proliferation of FTC cells via reducing miR-221-3p expression to enhance CDKN2B expression.</p><p><strong>Conclusion: </strong>GAS5 induced G0/G1 phase arrest and inhibited cell proliferation via targeting miR-221-3p/CDKN2B axis in FTC. Thus, GAS5 may be a potential therapeutic target for the treatment of FTC.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"289-300"},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000513338","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39239612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activin A Expressed in Rheumatoid Synovial Cells Downregulates TNFα-Induced CXCL10 Expression and Osteoclastogenesis.","authors":"Tatsuomi Kuranobu,&nbsp;Sho Mokuda,&nbsp;Katsuhiro Oi,&nbsp;Tadahiro Tokunaga,&nbsp;Kazutoshi Yukawa,&nbsp;Hiroki Kohno,&nbsp;Yusuke Yoshida,&nbsp;Shintaro Hirata,&nbsp;Eiji Sugiyama","doi":"10.1159/000506260","DOIUrl":"https://doi.org/10.1159/000506260","url":null,"abstract":"<p><strong>Objective: </strong>Activin A is known to be highly expressed in rheumatoid synovium. In the present study, we investigated the effect of inflammatory cytokines on activin A production and its role in rheumatoid inflammation using freshly prepared rheumatoid synovial cells (fresh-RSC).</p><p><strong>Methods: </strong>Fresh-RSC from patients with rheumatoid arthritis were obtained and stimulated with multiple cytokines for activin A production. Gene expression levels of activin A and inflammatory cytokines were determined by quantitative PCR (qPCR) analysis. An enzyme-linked immunosorbent assay (ELISA) was used to measure activin A and CXCL10 in culture supernatants. The osteoclasts generated from human peripheral monocytes by RANKL stimulation were identified by tartrate-resistant acid phosphatase staining and bone resorption assay using Osteo plate. The expression levels of NFATc1 and cathepsin K, critical intracellular proteins for osteoclastogenesis, were determined by Western blotting.</p><p><strong>Results: </strong>Activin A production in fresh-RSC was markedly enhanced by the synergistic effect of TGF-β1 with inflammatory cytokines, including TNFα, IL-1β, and IL-6. Activin A inhibited TNFα-induced CXCL10, an important chemoattractant for pathogen-activated T cells and monocytes of osteoclast precursors, but it did not affect the expression of inflammatory cytokines and chemokines. In addition, activin A directly inhibited the expression of NFATc1 and cathepsin K, as well as osteoclast formation in human samples.</p><p><strong>Conclusion: </strong>Our data indicated that TGF-β1 is involved in the expression of activin A at inflamed joints. Activin A mainly exerts an anti-inflammatory action, which prevents joint damage via the regulation of CXCL10 and osteoclastogenesis.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"198-207"},"PeriodicalIF":5.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000506260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37700678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutational Profiling of Driver Tumor Suppressor and Oncogenic Genes in Brazilian Malignant Pleural Mesotheliomas.","authors":"Nathália C Campanella,&nbsp;Eduardo Caetano Silva,&nbsp;Gustavo Dix,&nbsp;Fabiana de Lima Vazquez,&nbsp;Flávia Escremim de Paula,&nbsp;Gustavo N Berardinelli,&nbsp;Marcelo Balancin,&nbsp;Roger Chammas,&nbsp;Rossana V Mendoza Lopez,&nbsp;Henrique César S Silveira,&nbsp;Vera Luiza Capelozzi,&nbsp;Rui Manuel Reis","doi":"10.1159/000507373","DOIUrl":"https://doi.org/10.1159/000507373","url":null,"abstract":"<p><strong>Background: </strong>Malignant pleural mesothelioma (MPM) is a highly lethal disease comprising a heterogeneous group of tumors with challenging to predict biological behavior. The diagnosis is complex, and the histologic classification includes 2 major subtypes of MPM: epithelioid (∼60% of cases) and sarcomatous (∼20%). Its identification depends upon pathological investigation supported by clinical and radiological evidence and more recently ancillary molecular testing. Treatment options are currently limited, with no known targeted therapies available.</p><p><strong>Objectives: </strong>To elucidate the mutation profile of driver tumor suppressor and oncogenic genes in a cohort of Brazilian patients.</p><p><strong>Methods: </strong>We sequenced 16 driver genes in a series of 43 Brazilian malignant mesothelioma (MM) patients from 3 distinct Brazilian centers. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor tissue blocks, and the TERT promoter region was amplified by PCR followed by direct capillary sequencing. The Illumina TruSight Tumor 15 was used to evaluate 250 amplicons from 15 genes associated with solid tumors (AKT1, GNA11, NRAS, BRAF, GNAQ, PDGFRA, EGFR, KIT, PIK3CA, ERBB2, KRAS, RET, FOXL2, MET,and TP53). Library preparation with the TruSight Tumor 15 was performed before sequencing at the MiSeq platform. Data analysis was performed using Sophia DDM software.</p><p><strong>Results: </strong>Out of 43 MPM patients, 38 (88.4%) were epithelioid subtype and 5 (11.6%) were sarcomatoid histotype. Asbestos exposure was present in 15 (39.5%) patients with epithelioid MPM and 3 (60%) patients with sarcomatoid MPM. We found a TERT promoter mutation in 11.6% of MM, and the c.-146C>T mutation was the most common event. The next-generation sequencing was successful in 33 cases. A total of 18 samples showed at least 1 pathogenic, with a median of 1.8 variants, ranging from 1 to 6. The most mutated genes were TP53 and ERBB2 with 7 variants each, followed by NRAS BRAF, PI3KCA, EGFR and PDGFRA with 2 variants each. KIT, AKT1, and FOXL2 genes exhibited 1 variant each. Interestingly, 2 variants observed in the PDGFRA gene are classic imatinib-sensitive therapy.</p><p><strong>Conclusions: </strong>We concluded that Brazilian MPM harbor mutation in classic tumor suppressor and oncogenic genes, which might help in the guidance of personalized treatment of MPM.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"208-216"},"PeriodicalIF":5.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000507373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37901973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B7-H3 and B7-H4 Expression in Breast Cancer and Their Association with Clinicopathological Variables and T Cell Infiltration.","authors":"Nah Ihm Kim,&nbsp;Min Ho Park,&nbsp;Sun-Seog Kweon,&nbsp;Ji Shin Lee","doi":"10.1159/000505756","DOIUrl":"https://doi.org/10.1159/000505756","url":null,"abstract":"<p><strong>Objectives: </strong>B7-H3 and B7-H4 proteins are expressed in breast cancer tissues, but their relationships with respect to tumor immune surveillance and outcomes in breast cancer are not conclusive.</p><p><strong>Methods: </strong>We first examined B7-H3 and B7-H4 mRNA expression in the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. Next, mRNA and protein expression were assessed by RNAscope in situ hybridization (ISH) and immunohistochemistry in 10 pairs of breast cancer and matched normal tissues. Immunohistochemical staining of B7-H3, B7-H4, CD3, and CD8 was performed in tissue microarray slides containing 198 breast cancer samples. Association of B7-H3 and B7-H4 expression with survival was verified using the publicly accessible BreastMark tool.</p><p><strong>Results: </strong>B7-H3 and B7-H4 mRNA expression were significantly higher in breast cancer samples in the TCGA dataset than in normal breast tissues in the GTEx dataset. RNAscope ISH and immunohistochemistry showed that B7-H3 and B7-H4 mRNA and protein appeared to be mainly expressed in cancer cells. Expression of B7-H3 and B7-H4 tended to be associated with low-density scores of stromal tumor-infiltrating lymphocytes (TILs) as well as molecular subtypes. Expressions of B7-H3 and B7-H4 were negatively correlated with stromal CD3+ and CD8+ T cell infiltration density. B7-H3 and B7-H4 expression was not associated with survival, which was verified by BreastMark analysis.</p><p><strong>Conclusion: </strong>Expression levels of B7-H3 and B7-H4 were independent of clinical outcomes of breast cancer. There was an inverse relationship between the expression of B7-H3 and B7-H4 in breast cancer and the density of stromal TILs and CD8+ T lymphocytes. This inverse relationship may represent a promising target in the field of breast cancer immunotherapy.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"179-192"},"PeriodicalIF":5.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000505756","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37668103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}