Pub Date : 2024-11-22DOI: 10.1016/j.prp.2024.155732
Tamás Zombori , Ádám Ferenczi , Anita Sejben , Szintia Almási , Veronika Szelestei , Renáta Kószó , Tamás Lantos , Zsuzsanna Kahán , Gábor Cserni
Histological grade is a validated prognostic factor of breast cancer but may show alterations following neoadjuvant chemotherapy (NACT). Its reporting after NACT is recommended by several guidelines, but evidence of its retained prognostic impact is scarce. Patients treated with NACT followed by surgery and having sufficient residual tumour for the determination of grade were analysed for the survival effects of posttreatment grade (yG). Kaplan-Meier analyses and the log-rank test were applied, followed by the univariable and multivariable Cox proportional hazards models. The cohort comprised 355 patients with known yG, and 320 of them had also a pretreatment grade available. Pretreatment grade changed in 99/320 (31 %) cases following NACT, and downgrading was more common (n=78/320, 24 %) than upgrading (21/320, 7 %). Among 355 breast cancer patients, those with yG3 (poorly differentiated) tumours (n=155) had worse 5-year relapse-free and overall survival estimates than those with yG2 (n=169) or yG1 (n=31) tumours. This was also substantiated by univariable analysis; however, yG lost its significance in the multivariable model. Post-NACT histological grade has a prognostic impact, but does not seem to be an independent prognosticator in the post-NACT setting; however, these results lend support for its reporting by pathologists after primary systemic treatment.
{"title":"The prognostic value of histological grade determined after neoadjuvant chemotherapy of breast cancer","authors":"Tamás Zombori , Ádám Ferenczi , Anita Sejben , Szintia Almási , Veronika Szelestei , Renáta Kószó , Tamás Lantos , Zsuzsanna Kahán , Gábor Cserni","doi":"10.1016/j.prp.2024.155732","DOIUrl":"10.1016/j.prp.2024.155732","url":null,"abstract":"<div><div>Histological grade is a validated prognostic factor of breast cancer but may show alterations following neoadjuvant chemotherapy (NACT). Its reporting after NACT is recommended by several guidelines, but evidence of its retained prognostic impact is scarce. Patients treated with NACT followed by surgery and having sufficient residual tumour for the determination of grade were analysed for the survival effects of posttreatment grade (yG). Kaplan-Meier analyses and the log-rank test were applied, followed by the univariable and multivariable Cox proportional hazards models. The cohort comprised 355 patients with known yG, and 320 of them had also a pretreatment grade available. Pretreatment grade changed in 99/320 (31 %) cases following NACT, and downgrading was more common (n=78/320, 24 %) than upgrading (21/320, 7 %). Among 355 breast cancer patients, those with yG3 (poorly differentiated) tumours (n=155) had worse 5-year relapse-free and overall survival estimates than those with yG2 (n=169) or yG1 (n=31) tumours. This was also substantiated by univariable analysis; however, yG lost its significance in the multivariable model. Post-NACT histological grade has a prognostic impact, but does not seem to be an independent prognosticator in the post-NACT setting; however, these results lend support for its reporting by pathologists after primary systemic treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"265 ","pages":"Article 155732"},"PeriodicalIF":2.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701121","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}
Pub Date : 2024-11-20DOI: 10.1016/j.prp.2024.155731
Catherine Kollmann , Carolin Niklas , Karen Ernestus , Grit GR Hiller , Marius Hörner , Natalie Burkard , Christoph-Thomas Germer , Christoph Härtel , Thomas Meyer , Sina Bartfeld , Kirsten Glaser , Nicolas Schlegel
Necrotizing enterocolitis (NEC) is a major cause of mortality in preterm infants. Its pathophysiology remains poorly understood but intestinal epithelial barrier dysfunction contributes to the disease. We characterized junctional proteins in intestinal specimens from preterm infants. Samples from 27 patients with NEC and 20 patients with focal intestinal perforation (FIP) from the center of the specimens (affected) or the macroscopically healthy resection margins whenever available (non-affected) were collected. NEC patients displayed higher mortality and more commonly occurrence of impaired glucose homeostasis, patent ductus arteriosus, anemia and antibiotic treatment compared to FIP patients. Discrimination between NEC and FIP was not possible in affected areas based on H.E. staining using a newly developed scoring system. Immunofluorescence revealed reduced Claudin-3 in affected NEC samples and decreased Claudin-4 in affected FIP and all NEC samples. E-cadherin and Desmoglein-2 were reduced in a subgroup of the affected NEC samples. Plakophilin-2 was decreased in intestine affected by FIP and unaffected intestine in patients with NEC. In affected areas of NEC, Plakophilin-2 was completely lost. Plakoglobin reduction in affected NEC samples correlated with poor survival. This study provides novel insights into changes of junctional proteins in NEC, suggesting Claudin-3 and Plakophilin-2 as diagnostic markers to differentiate FIP from NEC and reduced Plakoglobin as a prognostic marker.
坏死性小肠结肠炎（NEC）是早产儿死亡的主要原因。人们对其病理生理学仍知之甚少，但肠道上皮屏障功能障碍是导致该病的原因之一。我们对早产儿肠道标本中的连接蛋白进行了鉴定。我们从 27 名 NEC 患者和 20 名局灶性肠穿孔（FIP）患者的标本中心（受影响）或宏观健康的切除边缘（非受影响）采集了样本。与 FIP 患者相比，NEC 患者的死亡率较高，且更常出现糖稳态受损、动脉导管未闭、贫血和抗生素治疗。根据使用新开发的评分系统进行的H.E.染色，无法在受影响区域区分NEC和FIP。免疫荧光显示，受影响的NEC样本中Claudin-3减少，而受影响的FIP和所有NEC样本中Claudin-4减少。E-cadherin和Desmoglein-2在受影响的NEC样本中减少。在受 FIP 影响的肠道和 NEC 患者未受影响的肠道中，Plakophilin-2 减少。在 NEC 受影响的区域，Plakophilin-2 完全消失。受影响的 NEC 样本中 Plakoglobin 的减少与存活率低有关。这项研究为了解 NEC 中连接蛋白的变化提供了新的视角，建议将 Claudin-3 和 Plakophilin-2 作为诊断标志物来区分 FIP 和 NEC，并将 Plakoglobin 的减少作为预后标志物。
{"title":"The phenotype of necrotizing enterocolitis correlates with distinct changes of intestinal junctional proteins","authors":"Catherine Kollmann , Carolin Niklas , Karen Ernestus , Grit GR Hiller , Marius Hörner , Natalie Burkard , Christoph-Thomas Germer , Christoph Härtel , Thomas Meyer , Sina Bartfeld , Kirsten Glaser , Nicolas Schlegel","doi":"10.1016/j.prp.2024.155731","DOIUrl":"10.1016/j.prp.2024.155731","url":null,"abstract":"<div><div>Necrotizing enterocolitis (NEC) is a major cause of mortality in preterm infants. Its pathophysiology remains poorly understood but intestinal epithelial barrier dysfunction contributes to the disease. We characterized junctional proteins in intestinal specimens from preterm infants. Samples from 27 patients with NEC and 20 patients with focal intestinal perforation (FIP) from the center of the specimens (affected) or the macroscopically healthy resection margins whenever available (non-affected) were collected. NEC patients displayed higher mortality and more commonly occurrence of impaired glucose homeostasis, patent ductus arteriosus, anemia and antibiotic treatment compared to FIP patients. Discrimination between NEC and FIP was not possible in affected areas based on H.E. staining using a newly developed scoring system. Immunofluorescence revealed reduced Claudin-3 in affected NEC samples and decreased Claudin-4 in affected FIP and all NEC samples. E-cadherin and Desmoglein-2 were reduced in a subgroup of the affected NEC samples. Plakophilin-2 was decreased in intestine affected by FIP and unaffected intestine in patients with NEC. In affected areas of NEC, Plakophilin-2 was completely lost. Plakoglobin reduction in affected NEC samples correlated with poor survival. This study provides novel insights into changes of junctional proteins in NEC, suggesting Claudin-3 and Plakophilin-2 as diagnostic markers to differentiate FIP from NEC and reduced Plakoglobin as a prognostic marker.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"265 ","pages":"Article 155731"},"PeriodicalIF":2.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695756","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}
SPRED2 (Sprouty-related, EVH1 domain-containing protein 2), a negative regulator of the ERK1/2 pathway, is downregulated in several cancers; however, the significance of SPRED2 expression in lung adenocarcinoma (LUAD) remains unclear. Here, we investigated the pathological expression of SPRED2 and its relationship with ERK1/2 activation (ERK1/2 phosphorylation), Ki67 index and clinicopathological features in 77 LUAD tissues from clinical patients. Immunohistochemically, SPRED2 expression was decreased in invasive adenocarcinoma (IA) compared to adenocarcinoma in situ (AIS). There was a negative correlation between SPRED2 expression and pERK1/2 levels and a positive correlation between SPRED2 expression and Ki67 index. In the database analysis, the survival probability was higher in patients with higher SPRED2 expression than in those with lower expression. In vitro, SPRED2 deletion increased cell proliferation, migration and invasion of three LUAD cell lines (A549:KRAS mutation, H1993:METamplification, and HCC4006:EGFR mutation), whereas SPRED2 overexpression decreased these responses. Thus, SPRED2 appears to be a regulator of LUAD progression and a potential target for the treatment of LUAD.
{"title":"Expression of SPRED2 in the lung adenocarcinoma","authors":"Yoko Ota , Tong Gao , Masayoshi Fujisawa , I.Wayan Sumardika , Masakiyo Sakaguchi , Shinichi Toyooka , Teizo Yoshimura , Akihiro Matsukawa","doi":"10.1016/j.prp.2024.155721","DOIUrl":"10.1016/j.prp.2024.155721","url":null,"abstract":"<div><div>SPRED2 (Sprouty-related, EVH1 domain-containing protein 2), a negative regulator of the ERK1/2 pathway, is downregulated in several cancers; however, the significance of SPRED2 expression in lung adenocarcinoma (LUAD) remains unclear. Here, we investigated the pathological expression of SPRED2 and its relationship with ERK1/2 activation (ERK1/2 phosphorylation), Ki67 index and clinicopathological features in 77 LUAD tissues from clinical patients. Immunohistochemically, SPRED2 expression was decreased in invasive adenocarcinoma (IA) compared to adenocarcinoma in situ (AIS). There was a negative correlation between SPRED2 expression and pERK1/2 levels and a positive correlation between SPRED2 expression and Ki67 index. In the database analysis, the survival probability was higher in patients with higher SPRED2 expression than in those with lower expression. In vitro, SPRED2 deletion increased cell proliferation, migration and invasion of three LUAD cell lines (A549:KRAS mutation, H1993:METamplification, and HCC4006:EGFR mutation), whereas SPRED2 overexpression decreased these responses. Thus, SPRED2 appears to be a regulator of LUAD progression and a potential target for the treatment of LUAD.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"265 ","pages":"Article 155721"},"PeriodicalIF":2.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701176","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}
Recently, our research group reported an upregulated expression profile of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), key enzymes involved in hydrogen sulfide (H2S) production, in triple-negative breast cancer (TNBC) patients. However, the regulatory mechanisms underlying such altered expression patterns are not yet fully understood. In this study, we focused on the role of the STAT3/CSE/H2S axis and the potential involvement of non-coding RNAs (ncRNAs), including long and short ncRNAs, in modulating this pivotal pathway. The results revealed that STAT3 was upregulated and positively correlated with CSE expression in BC patients. Additionally, the lncRNA MALAT-1 was found to regulate STAT3 expression, indirectly influencing CSE levels. Furthermore, we explored the interplay between the IGF-1R as a gatekeeper for JAK/STAT pathway and accordingly its impact on the STAT3/CSE/H2S axis in TNBC cell lines. Our results demonstrated that miR-486–5p, a tumor suppressor miRNA, directly targets IGF-1R, leading to the downstream suppression of STAT3 and CSE in MDA-MB-231 cells. To identify a direct upstream repressor of CSE and CBS, we conducted an in silico analysis and identified miR-30a-5p as a promising candidate. When ectopically expressed, miR-30a-5p was downregulated in BC tissues and effectively suppressed CSE and CBS expression. In conclusion, this study revealed novel regulatory mechanisms involved in CSE and CBS expression in TNBC patients and cell lines. Abolishing H2S-synthesizing machinery, particularly via miR-30a-5p, may represent a promising therapeutic strategy for TNBC patients.
最近，我们的研究小组报告了三阴性乳腺癌（TNBC）患者体内胱硫醚γ-赖氨酸酶（CSE）和胱硫醚β-合成酶（CBS）表达上调的情况，这两种酶是参与硫化氢（H2S）生成的关键酶。然而，这种表达模式改变背后的调控机制尚未完全明了。在这项研究中，我们重点研究了 STAT3/CSE/H2S 轴的作用以及非编码 RNA（ncRNA）（包括长短 ncRNA）在调节这一关键通路中的潜在参与。结果发现，STAT3在BC患者中上调，并与CSE的表达呈正相关。此外，研究还发现lncRNA MALAT-1可调控STAT3的表达，间接影响CSE水平。此外，我们还探讨了IGF-1R作为JAK/STAT通路的看门人之间的相互作用，并据此探讨了它对TNBC细胞系中STAT3/CSE/H2S轴的影响。我们的研究结果表明，肿瘤抑制miRNA miR-486-5p直接靶向IGF-1R，导致MDA-MB-231细胞中STAT3和CSE受到下游抑制。为了确定CSE和CBS的直接上游抑制因子，我们进行了一项硅学分析，发现miR-30a-5p是一个很有希望的候选因子。当异位表达时，miR-30a-5p 在 BC 组织中下调，并有效抑制了 CSE 和 CBS 的表达。总之，这项研究揭示了TNBC患者和细胞系中CSE和CBS表达的新调控机制。废除H2S合成机制，特别是通过miR-30a-5p，可能是治疗TNBC患者的一种有前途的策略。
{"title":"Direct and indirect modulation of STAT3/CSE/H2S axis in triple negative breast cancer by non-coding RNAs: MALAT-1 lncRNA, miR-486–5p and miR-30a-5p","authors":"Rana A. Youness , Nour Khater , Aisha El-Khouly , Heba Nafea , Tamer Manie , Danira Habashy , Mohamed Z. Gad","doi":"10.1016/j.prp.2024.155729","DOIUrl":"10.1016/j.prp.2024.155729","url":null,"abstract":"<div><div>Recently, our research group reported an upregulated expression profile of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), key enzymes involved in hydrogen sulfide (H<sub>2</sub>S) production, in triple-negative breast cancer (TNBC) patients. However, the regulatory mechanisms underlying such altered expression patterns are not yet fully understood. In this study, we focused on the role of the STAT3/CSE/H<sub>2</sub>S axis and the potential involvement of non-coding RNAs (ncRNAs), including long and short ncRNAs, in modulating this pivotal pathway. The results revealed that STAT3 was upregulated and positively correlated with CSE expression in BC patients. Additionally, the lncRNA MALAT-1 was found to regulate STAT3 expression, indirectly influencing CSE levels. Furthermore, we explored the interplay between the IGF-1R as a gatekeeper for JAK/STAT pathway and accordingly its impact on the STAT3/CSE/H<sub>2</sub>S axis in TNBC cell lines. Our results demonstrated that miR-486–5p, a tumor suppressor miRNA, directly targets IGF-1R, leading to the downstream suppression of STAT3 and CSE in MDA-MB-231 cells. To identify a direct upstream repressor of CSE and CBS, we conducted an <em>in silico</em> analysis and identified miR-30a-5p as a promising candidate. When ectopically expressed, miR-30a-5p was downregulated in BC tissues and effectively suppressed CSE and CBS expression. In conclusion, this study revealed novel regulatory mechanisms involved in CSE and CBS expression in TNBC patients and cell lines. Abolishing H<sub>2</sub>S-synthesizing machinery, particularly via miR-30a-5p, may represent a promising therapeutic strategy for TNBC patients.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"265 ","pages":"Article 155729"},"PeriodicalIF":2.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701122","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}
Pub Date : 2024-11-19DOI: 10.1016/j.prp.2024.155726
Georgi Lukose , Majd Al Assaad , Jordan H. Driskill , Max F. Levine , Gunes Gundem , Alissa Semaan , David C. Wilkes , Nitsana A. Spigland , Juan S. Medina-Martínez , Andrea Sboner , Olivier Elemento , José Jessurun , Juan Miguel Mosquera
Malignant biphasic tumors of the lungs are rare, more so in the pediatric population. Here, we present the whole-genome characterization of a pleuropulmonary blastoma Type III and an unclassified biphasic thoracic embryonal neoplasm. The pleuropulmonary blastoma harbored pathogenic DICER1 germline and somatic mutations, and additional somatic variants in TP53 and BCOR. The other malignant tumor demonstrated a t(11;19) balanced translocation with a YAP1::LEUTX fusion that was confirmed by fluorescence in situ hybridization. No DICER1 germline or somatic mutation was present. YAP1 and LEUTX have been implicated in tumorigenesis of various neoplasms, and YAP1 fusion genes are an emerging oncogenic entity in a variety of malignancies. In this study we highlight the importance of whole-genome characterization of rare and unclassified tumors to identify biologic mechanisms and potential therapeutic targets.
{"title":"Whole genome profiling of rare pediatric thoracic tumors elucidates a YAP1::LEUTX fusion in an unclassified biphasic embryonal neoplasm","authors":"Georgi Lukose , Majd Al Assaad , Jordan H. Driskill , Max F. Levine , Gunes Gundem , Alissa Semaan , David C. Wilkes , Nitsana A. Spigland , Juan S. Medina-Martínez , Andrea Sboner , Olivier Elemento , José Jessurun , Juan Miguel Mosquera","doi":"10.1016/j.prp.2024.155726","DOIUrl":"10.1016/j.prp.2024.155726","url":null,"abstract":"<div><div>Malignant biphasic tumors of the lungs are rare, more so in the pediatric population. Here, we present the whole-genome characterization of a pleuropulmonary blastoma Type III and an unclassified biphasic thoracic embryonal neoplasm. The pleuropulmonary blastoma harbored pathogenic <em>DICER1</em> germline and somatic mutations, and additional somatic variants in <em>TP53</em> and <em>BCOR</em>. The other malignant tumor demonstrated a t(11;19) balanced translocation with a <em>YAP1::LEUTX</em> fusion that was confirmed by fluorescence <em>in situ</em> hybridization. No <em>DICER1</em> germline or somatic mutation was present. <em>YAP1</em> and <em>LEUTX</em> have been implicated in tumorigenesis of various neoplasms, and <em>YAP1</em> fusion genes are an emerging oncogenic entity in a variety of malignancies. In this study we highlight the importance of whole-genome characterization of rare and unclassified tumors to identify biologic mechanisms and potential therapeutic targets.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155726"},"PeriodicalIF":2.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682387","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}
The performance of cell blocks (CBs) can vary significantly depending on the specimen collection and processing techniques used. This study compared the efficiency of three distinct specimen collection methods for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples.
Materials and methods
From June 2021 to June 2023, the study involved 1450 patients who underwent EBUS-TBNA, resulting in the sampling of 1941 lesions. For these samples, three distinct specimen processing methods were employed to prepare tissue coagulum clot-based CBs. Specifically, the filter paper method was employed in 470 cases (yielding 626 samples), the centrifugation method in 500 cases (yielding 673 samples), and the funnel filtration method in 480 cases (yielding 642 samples).
Results
Out of these 1941 samples, the diagnostic yield for samples obtained using filter paper, centrifugation, and funnel filtration methods was 84.7 %, 87.7 %, and 92.5 %, respectively. In the subgroup of patients diagnosed with non-small cell lung cancer, the adequacy rate for molecular testing in samples processed through filter paper, centrifugation, and funnel filtration methods was 57.7 %, 82.0 %, and 88.3 %, respectively. In the centrifugation group, the combination of the CBs and cell pellet achieved an adequacy rate of 96.5 %.
Discussion
The cellular yield of CBs from EBUS-TBNA was significantly enhanced using centrifugation and funnel filtration methods. The funnel filtration method offered a more convenient and cost-effective approach, reducing cellular loss due to sample dispersion in the fixative medium. The use of the centrifugation method to prepare CBs, along with the retrieval of cell pellets from the residual fixative medium, can maximize the specimen adequacy rate for molecular testing.
{"title":"Comparison of three specimen collection techniques in tissue coagulum clot-based cell block preparation of endobronchial ultrasound-guided transbronchial needle aspiration","authors":"Zeyun Lin , Lixi Huang , Shiqi Tang , Anzi Tan , Chunli Tang , Yingying Gu , Jiangyu Zhang , Juhong Jiang","doi":"10.1016/j.prp.2024.155730","DOIUrl":"10.1016/j.prp.2024.155730","url":null,"abstract":"<div><h3>Objectives</h3><div>The performance of cell blocks (CBs) can vary significantly depending on the specimen collection and processing techniques used. This study compared the efficiency of three distinct specimen collection methods for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples.</div></div><div><h3>Materials and methods</h3><div>From June 2021 to June 2023, the study involved 1450 patients who underwent EBUS-TBNA, resulting in the sampling of 1941 lesions. For these samples, three distinct specimen processing methods were employed to prepare tissue coagulum clot-based CBs. Specifically, the filter paper method was employed in 470 cases (yielding 626 samples), the centrifugation method in 500 cases (yielding 673 samples), and the funnel filtration method in 480 cases (yielding 642 samples).</div></div><div><h3>Results</h3><div>Out of these 1941 samples, the diagnostic yield for samples obtained using filter paper, centrifugation, and funnel filtration methods was 84.7 %, 87.7 %, and 92.5 %, respectively. In the subgroup of patients diagnosed with non-small cell lung cancer, the adequacy rate for molecular testing in samples processed through filter paper, centrifugation, and funnel filtration methods was 57.7 %, 82.0 %, and 88.3 %, respectively. In the centrifugation group, the combination of the CBs and cell pellet achieved an adequacy rate of 96.5 %.</div></div><div><h3>Discussion</h3><div>The cellular yield of CBs from EBUS-TBNA was significantly enhanced using centrifugation and funnel filtration methods. The funnel filtration method offered a more convenient and cost-effective approach, reducing cellular loss due to sample dispersion in the fixative medium. The use of the centrifugation method to prepare CBs, along with the retrieval of cell pellets from the residual fixative medium, can maximize the specimen adequacy rate for molecular testing.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"265 ","pages":"Article 155730"},"PeriodicalIF":2.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695755","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}
Pub Date : 2024-11-16DOI: 10.1016/j.prp.2024.155724
Mieke R. Van Bockstal , Marie-Caroline Depelsemaeker , Lina Daoud , Quitterie Fontanges , Aline Francois , Yves Guiot , Anne-France Dekairelle , Dominique Dubois , Cédric Van Marcke , Eléonore Longton , Francois P. Duhoux , Hilde Vernaeve , Martine Berlière , Giuseppe Floris , Christine Galant
Trophoblast cell-surface antigen 2 (TROP2), a transmembrane receptor expressed in many carcinomas, is a target for novel antibody-drug conjugates such as sacituzumab govitecan. TROP2-targeted therapy is used for unresectable locally advanced or metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancers. The role of TROP2 as a predictive marker is yet unclear. Standardized interpretation criteria for TROP2 immunohistochemistry (IHC) are lacking. Here, we compared three antibody clones and two methods for semi-quantitative assessment, aiming to establish reproducible evaluation criteria. First, TROP2 IHC was performed on normal tissues and nine breast cancers, using the BSB-148, EPR20043 and SP293 clones. EPR20043 was selected for subsequent evaluation in 69 breast cancers without pathological complete response to neoadjuvant chemotherapy (NAC). Four pathologists applied the ASCO/CAP guidelines for HER2 IHC testing (designated as the ‘membrane score’) and the H-score. All H-scores were categorized as low (0−100), intermediate (101−200) and high (201−300). Although the membrane scores strongly correlated with the categorized H-scores, the latter showed higher interobserver variability. Next, TROP2 IHC was performed on 94 breast cancer metastases and evaluated by six pathologists, confirming the strong correlation between the membrane scores and H-scores. In metastases, the interobserver variability was similar for both methods. Our observations support the application of the HER2 ASCO/CAP guidelines for semi-quantitative evaluation of membranous TROP2 protein expression, as this method strongly correlates with the H-score and is less prone to interobserver variability in post-NAC breast resections. Future studies should investigate the association between the TROP2 membrane score and response to TROP2-targeted therapy.
{"title":"Evaluation of trophoblast cell surface antigen-2 (TROP2) protein expression in chemotherapy-resistant and metastatic breast carcinomas","authors":"Mieke R. Van Bockstal , Marie-Caroline Depelsemaeker , Lina Daoud , Quitterie Fontanges , Aline Francois , Yves Guiot , Anne-France Dekairelle , Dominique Dubois , Cédric Van Marcke , Eléonore Longton , Francois P. Duhoux , Hilde Vernaeve , Martine Berlière , Giuseppe Floris , Christine Galant","doi":"10.1016/j.prp.2024.155724","DOIUrl":"10.1016/j.prp.2024.155724","url":null,"abstract":"<div><div>Trophoblast cell-surface antigen 2 (TROP2), a transmembrane receptor expressed in many carcinomas, is a target for novel antibody-drug conjugates such as sacituzumab govitecan. TROP2-targeted therapy is used for unresectable locally advanced or metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancers. The role of TROP2 as a predictive marker is yet unclear. Standardized interpretation criteria for TROP2 immunohistochemistry (IHC) are lacking. Here, we compared three antibody clones and two methods for semi-quantitative assessment, aiming to establish reproducible evaluation criteria. First, TROP2 IHC was performed on normal tissues and nine breast cancers, using the BSB-148, EPR20043 and SP293 clones. EPR20043 was selected for subsequent evaluation in 69 breast cancers without pathological complete response to neoadjuvant chemotherapy (NAC). Four pathologists applied the ASCO/CAP guidelines for HER2 IHC testing (designated as the ‘membrane score’) and the H-score. All H-scores were categorized as low (0−100), intermediate (101−200) and high (201−300). Although the membrane scores strongly correlated with the categorized H-scores, the latter showed higher interobserver variability. Next, TROP2 IHC was performed on 94 breast cancer metastases and evaluated by six pathologists, confirming the strong correlation between the membrane scores and H-scores. In metastases, the interobserver variability was similar for both methods. Our observations support the application of the HER2 ASCO/CAP guidelines for semi-quantitative evaluation of membranous TROP2 protein expression, as this method strongly correlates with the H-score and is less prone to interobserver variability in post-NAC breast resections. Future studies should investigate the association between the TROP2 membrane score and response to TROP2-targeted therapy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155724"},"PeriodicalIF":2.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687664","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}
Pub Date : 2024-11-16DOI: 10.1016/j.prp.2024.155727
Xiyu Liu , Zuolin Shi , Xuantong Liu , Yuan Cao , Xinyu Yang , Jiaming Liu , Tianqi Xu , Weiyi Yang , Ligang Chen , Zheng Zou , Qingge Jia , Mingyang Li
Background
Glioblastoma (GBM) poses formidable challenges due to its high malignancy and therapeutic resistance and still exhibits dismal 5-year survival rates, high recurrence propensity, and limited treatment modalities. There is an acute need for innovative treatments for recurrent glioblastoma due to the lack of established protocols. This necessity is driving research into the cellular underpinnings that initiate and drive the disease forward, aiming to discover groundbreaking targets for therapy that could enhance the efficacy of medical interventions.
Methods
Patient-derived glioblastoma stem cells (GSCs) were harvested and isolated. Subsequently, PDCD6 expression was quantified through both western blotting (WB) and real-time PCR (RT-PCR) techniques. The stem-like properties of the GSCs were evaluated using sphere-forming assays. All gathered data, inclusive of TCGA datasets, were analyzed using SPSS (IBM) version 23.0.
Results
Elevated PDCD6 expression characterized classical GBM tumor tissues. PDCD6 overexpression significantly correlated with diminished overall survival in GBM patients, emerging as an independent prognostic indicator. Notably, primary GBM cells exhibited heightened PDCD6 levels in GSCs compared to NSTCs. Moreover, alterations in stemness markers paralleled PDCD6 modulation, where PDCD6 knockdown attenuated tumor size in GSCs.
Conclusion
Our findings illuminate PDCD6's role in fostering stemness within classical GBM, hinting at its potential as a therapeutic target.
{"title":"The role of PDCD6 in stemness maintenance of Glioblastoma","authors":"Xiyu Liu , Zuolin Shi , Xuantong Liu , Yuan Cao , Xinyu Yang , Jiaming Liu , Tianqi Xu , Weiyi Yang , Ligang Chen , Zheng Zou , Qingge Jia , Mingyang Li","doi":"10.1016/j.prp.2024.155727","DOIUrl":"10.1016/j.prp.2024.155727","url":null,"abstract":"<div><h3>Background</h3><div>Glioblastoma (GBM) poses formidable challenges due to its high malignancy and therapeutic resistance and still exhibits dismal 5-year survival rates, high recurrence propensity, and limited treatment modalities. There is an acute need for innovative treatments for recurrent glioblastoma due to the lack of established protocols. This necessity is driving research into the cellular underpinnings that initiate and drive the disease forward, aiming to discover groundbreaking targets for therapy that could enhance the efficacy of medical interventions.</div></div><div><h3>Methods</h3><div>Patient-derived glioblastoma stem cells (GSCs) were harvested and isolated. Subsequently, PDCD6 expression was quantified through both western blotting (WB) and real-time PCR (RT-PCR) techniques. The stem-like properties of the GSCs were evaluated using sphere-forming assays. All gathered data, inclusive of TCGA datasets, were analyzed using SPSS (IBM) version 23.0.</div></div><div><h3>Results</h3><div>Elevated PDCD6 expression characterized classical GBM tumor tissues. PDCD6 overexpression significantly correlated with diminished overall survival in GBM patients, emerging as an independent prognostic indicator. Notably, primary GBM cells exhibited heightened PDCD6 levels in GSCs compared to NSTCs. Moreover, alterations in stemness markers paralleled PDCD6 modulation, where PDCD6 knockdown attenuated tumor size in GSCs.</div></div><div><h3>Conclusion</h3><div>Our findings illuminate PDCD6's role in fostering stemness within classical GBM, hinting at its potential as a therapeutic target.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155727"},"PeriodicalIF":2.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676651","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}
Pub Date : 2024-11-14DOI: 10.1016/j.prp.2024.155722
Annikka Weissferdt, Cesar A. Moran
We describe 3 patients with clear cell stromal tumor (CCST) of the lung, all of whom presented with multifocal disease. The patients were 2 men and 1 woman aged 47–58 years (mean, 54 years). Two patients had evidence of autoimmune disease and their pulmonary disease was an incidental finding; one patient presented with non-specific respiratory symptoms. Radiologic imaging revealed multiple pulmonary nodules in all patients. Histologically, the tumors were solid-cystic and composed of cytologically bland, medium-sized ovoid to spindle cells with eosinophilic to clear cytoplasm arranged in a subtle nested pattern. These tumor cells were set in a highly vascularized stroma. Occasional cytologic atypia with multinucleated tumor cells was noted but mitotic activity was low. An infiltrate of mixed inflammatory cells was apparent in all tumors. Immunohistochemical analysis demonstrated diffuse expression of vimentin and TFE3 in all cases. Next generation sequencing revealed the presence of YAP1::TFE3 fusion in 1/1 case. All patients have remained alive albeit with stable or progressive disease, 24–66 months after diagnosis. These cases highlight the existence of multifocal pulmonary CCST and seem to support the notion that multifocality in CCST may be associated with more protracted clinical course. Awareness of the existence of multifocal pattern is important for patient management and prognosis.
{"title":"Clear cell stromal tumor of the lung: Report of 3 cases with emphasis on multifocal tumors","authors":"Annikka Weissferdt, Cesar A. Moran","doi":"10.1016/j.prp.2024.155722","DOIUrl":"10.1016/j.prp.2024.155722","url":null,"abstract":"<div><div>We describe 3 patients with clear cell stromal tumor (CCST) of the lung, all of whom presented with multifocal disease. The patients were 2 men and 1 woman aged 47–58 years (mean, 54 years). Two patients had evidence of autoimmune disease and their pulmonary disease was an incidental finding; one patient presented with non-specific respiratory symptoms. Radiologic imaging revealed multiple pulmonary nodules in all patients. Histologically, the tumors were solid-cystic and composed of cytologically bland, medium-sized ovoid to spindle cells with eosinophilic to clear cytoplasm arranged in a subtle nested pattern. These tumor cells were set in a highly vascularized stroma. Occasional cytologic atypia with multinucleated tumor cells was noted but mitotic activity was low. An infiltrate of mixed inflammatory cells was apparent in all tumors. Immunohistochemical analysis demonstrated diffuse expression of vimentin and TFE3 in all cases. Next generation sequencing revealed the presence of <em>YAP1::TFE3</em> fusion in 1/1 case. All patients have remained alive albeit with stable or progressive disease, 24–66 months after diagnosis. These cases highlight the existence of multifocal pulmonary CCST and seem to support the notion that multifocality in CCST may be associated with more protracted clinical course. Awareness of the existence of multifocal pattern is important for patient management and prognosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155722"},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142661981","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":"Corrigendum to \"A review on the role of KCNQ1OT1 lncRNA in human disorders\" [Pathol. - Res. Pract. 255 (2024) 155188].","authors":"Mohammad Taheri, Zeinab Shirvani-Farsani, Atefeh Harsij, Mohadeseh Fathi, Sheyda Khalilian, Soudeh Ghafouri-Fard, Aria Baniahmad","doi":"10.1016/j.prp.2024.155723","DOIUrl":"https://doi.org/10.1016/j.prp.2024.155723","url":null,"abstract":"","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":" ","pages":"155723"},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639436","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}
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