Journal of Pathology Clinical Research最新文献

{"title":"Anaplastic and poorly differentiated thyroid carcinomas: genetic evidence of high-grade transformation from differentiated thyroid carcinoma","authors":"Haiyan Gu,&nbsp;Jingnan Wang,&nbsp;Wenwen Ran,&nbsp;Guangqi Li,&nbsp;Shasha Hu,&nbsp;Han Zhao,&nbsp;Xiaonan Wang,&nbsp;Jigang Wang","doi":"10.1002/cjp2.356","DOIUrl":"https://doi.org/10.1002/cjp2.356","url":null,"abstract":"<p>Anaplastic thyroid carcinoma (ATC) is the most advanced and aggressive thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) lacks anaplastic histology but has lost architectural and cytologic differentiation. Only a few studies have focused on the genetic relationship between the two advanced carcinomas and coexisting differentiated thyroid carcinomas (DTCs). In the present study, we investigated clinicopathologic features and genetic profiles in 57 ATC and PDTC samples, among which 33 cases had concomitant DTC components or DTC history. We performed immunohistochemistry for BRAF V600E, p53, and PD-L1 expression, Sanger sequencing for <i>TERT</i> promoter and <i>RAS</i> mutations, and fluorescence <i>in situ</i> hybridization for <i>ALK</i> and <i>RET</i> rearrangements. We found that ATCs and PDTCs shared similar gene alterations to their coexisting DTCs, and most DTCs were aggressive subtypes harboring frequent <i>TERT</i> promoter mutations. A significantly higher proportion of ATCs expressed p53 and PD-L1, and a lower proportion expressed PAX-8 and TTF-1, than the coexisting DTCs. Our findings provide more reliable evidence that ATCs and PDTCs are derived from DTCs.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.356","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139494591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint CD161/LLT1-associated immunological landscape and diagnostic value in oral squamous cell carcinoma","authors":"Xinyang Hu,&nbsp;Yuexin Dong,&nbsp;Shixin Xie,&nbsp;Yuxian Song,&nbsp;Chenhang Yu,&nbsp;Yijia He,&nbsp;Zhiyong Wang,&nbsp;Qingang Hu,&nbsp;Yanhong Ni,&nbsp;Liang Ding","doi":"10.1002/cjp2.353","DOIUrl":"https://doi.org/10.1002/cjp2.353","url":null,"abstract":"<p>An active host adaptive response is characterized by the existence of programmed cell death protein 1 (PD-1)⁺/IFN-γ⁺ cytotoxic T cells and IFN-γ-induced PD-L1⁺ tumor cells (TCs), which predicts high response rate to anti-PD-1/L1 therapy. Recently, CD161 and its ligand LLT1 (CLEC2D) have been identified as an emerging checkpoint for immunotherapy. Clarifying its heterogeneous clinical expression pattern and its immune landscape is a prerequisite for maximizing the response rate of CD161 blockade therapy in a specific population of oral squamous cell carcinoma (OSCC) patients. Here, we investigated the expression pattern of CD161/LLT1 and its association with major immunocytes (T cells, B cells, NK cells, and macrophages) by multiplex immunofluorescence, immunohistochemistry, and flow cytometry in 109 OSCC tissues and 102 peripheral blood samples. TCs showed higher LLT1 levels than tumor infiltrating lymphocytes (TILs), whereas CD161 was highly expressed in CD8⁺ T cells at the tumor front, which was decreased in paracancerous tissue. High expression of TC-derived LLT1 (LLT1^TC) conferred poor clinical outcomes, whereas higher CD161⁺ and LLT1⁺ TILs were associated with better prognosis. Meanwhile, patients with high LLT1^TC showed a decreased ratio of CD8⁺/Foxp3⁺ T cells <i>in situ</i>, but CD161⁺ TILs correlated with more peripheral CD3⁺ T cells. Interestingly, treatment of OSCC patients with nivolumab (anti-PD-1) could restore tumoral CD161/LLT1 signal. Furthermore, an OSCC subgroup characterized by high LLT1⁺ TCs and low CD161⁺CD8⁺ T cells showed fewer peripheral T cells and a higher risk of lymph node metastasis, leading to a shorter 5-year survival time (29%). More LLT1^TC at the invasive front was another risk characteristic of exhausted T cells. In conclusion, in view of this heterogeneity, the LLT1/CD161 distribution pattern should be determined before CD161-based immunotherapy.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.353","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139480551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic heterogeneity at baseline is associated with T790M resistance mutations in EGFR-mutated lung cancer treated with the first-/second-generation tyrosine kinase inhibitors","authors":"Michael Menzel,&nbsp;Martina Kirchner,&nbsp;Klaus Kluck,&nbsp;Markus Ball,&nbsp;Susanne Beck,&nbsp;Michael Allgäuer,&nbsp;Christin Assmann,&nbsp;Johannes Schnorbach,&nbsp;Anna-Lena Volckmar,&nbsp;Timothy Kwang Yong Tay,&nbsp;Hannah Goldschmid,&nbsp;Daniel SW Tan,&nbsp;Michael Thomas,&nbsp;Daniel Kazdal,&nbsp;Jan Budczies,&nbsp;Albrecht Stenzinger,&nbsp;Petros Christopoulos","doi":"10.1002/cjp2.354","DOIUrl":"https://doi.org/10.1002/cjp2.354","url":null,"abstract":"<p>This study analyzed whether extended molecular profiling can predict the development of epidermal growth factor receptor (<i>EGFR</i>) gene T790M mutation, which is the most frequent resistance alteration in non-small cell lung cancer (NSCLC) after treatment with the first-/second-generation (1G/2G) EGFR inhibitors (tyrosine kinase inhibitors [TKIs]), but only weakly associated with clinical characteristics. Whole exome sequencing (WES) was performed on pretreatment tumor tissue with matched normal samples from NSCLC patients with (<i>n</i> = 25, detected in tissue or blood rebiopsies) or without (<i>n</i> = 14, negative tissue rebiopsies only) subsequent <i>EGFR</i> p.T790M mutation after treatment with 1G/2G EGFR TKI. Several complex genetic biomarkers were assessed using bioinformatic methods. After treatment with first-line afatinib (44%) or erlotinib/gefitinib (56%), median progression-free survival and overall survival were 12.1 and 33.7 months, respectively. Clinical and tumor genetic characteristics, including age (median, 66 years), sex (74% female), smoking (69% never/light smokers), <i>EGFR</i> mutation type (72% exon 19 deletions), and <i>TP53</i> mutations (41%) were not significantly associated with T790M mutation (<i>p</i> &gt; 0.05). By contrast, complex biomarkers including tumor mutational burden, the clock-like mutation signature SBS1 + 5, tumor ploidy, and markers of subclonality including mutant-allele tumor heterogeneity, subclonal copy number changes, and median tumor-adjusted variant allele frequency were significantly higher at baseline in tumors with subsequent T790M mutation (all <i>p</i> &lt; 0.05). Each marker alone could predict subsequent development of T790M with an area under the curve (AUC) of 0.72–0.77, but the small number of cases did not allow confirmation of better performance for biomarker combinations in leave-one-out cross-validated logistic regression (AUC 0.69, 95% confidence interval: 0.50–0.87). Extended molecular profiling with WES at initial diagnosis reveals several complex biomarkers associated with subsequent development of T790M resistance mutation in NSCLC patients receiving first-/second-generation TKIs as the first-line therapy. Larger prospective studies will be necessary to define a forecasting model.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139480552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A robust model training strategy using hard negative mining in a weakly labeled dataset for lymphatic invasion in gastric cancer","authors":"Jonghyun Lee,&nbsp;Sangjeong Ahn,&nbsp;Hyun-Soo Kim,&nbsp;Jungsuk An,&nbsp;Jongmin Sim","doi":"10.1002/cjp2.355","DOIUrl":"10.1002/cjp2.355","url":null,"abstract":"<p>Gastric cancer is a significant public health concern, emphasizing the need for accurate evaluation of lymphatic invasion (LI) for determining prognosis and treatment options. However, this task is time-consuming, labor-intensive, and prone to intra- and interobserver variability. Furthermore, the scarcity of annotated data presents a challenge, particularly in the field of digital pathology. Therefore, there is a demand for an accurate and objective method to detect LI using a small dataset, benefiting pathologists. In this study, we trained convolutional neural networks to classify LI using a four-step training process: (1) weak model training, (2) identification of false positives, (3) hard negative mining in a weakly labeled dataset, and (4) strong model training. To overcome the lack of annotated datasets, we applied a hard negative mining approach in a weakly labeled dataset, which contained only final diagnostic information, resembling the typical data found in hospital databases, and improved classification performance. Ablation studies were performed to simulate the lack of datasets and severely unbalanced datasets, further confirming the effectiveness of our proposed approach. Notably, our results demonstrated that, despite the small number of annotated datasets, efficient training was achievable, with the potential to extend to other image classification approaches used in medicine.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.355","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic tuft cell expansion during gastric metaplasia and dysplasia","authors":"Bogun Jang,&nbsp;Hyesung Kim,&nbsp;Su-Hyung Lee,&nbsp;Yoonkyung Won,&nbsp;Izumi Kaji,&nbsp;Robert J Coffey,&nbsp;Eunyoung Choi,&nbsp;James R Goldenring","doi":"10.1002/cjp2.352","DOIUrl":"10.1002/cjp2.352","url":null,"abstract":"<p>Tuft cells are chemosensory cells associated with luminal homeostasis, immune response, and tumorigenesis in the gastrointestinal tract. We aimed to elucidate alterations in tuft cell populations during gastric atrophy and tumorigenesis in humans with correlative comparison to relevant mouse models. Tuft cell distribution was determined in human stomachs from organ donors and in gastric pathologies including Ménétrier's disease, <i>Helicobacter pylori</i> gastritis, intestinal metaplasia (IM), and gastric tumors. Tuft cell populations were examined in <i>Lrig1-Kras</i>^<i>G12D</i>, <i>Mist1-Kras</i>^<i>G12D</i>, and MT-TGFα mice. Tuft cells were evenly distributed throughout the entire normal human stomach, primarily concentrated in the isthmal region in the fundus. Ménétrier's disease stomach showed increased tuft cells. Similarly, Lrig1-Kras mice and mice overexpressing TGFα showed marked foveolar hyperplasia and expanded tuft cell populations. Human stomach with IM or dysplasia also showed increased tuft cell numbers. Similarly, Mist1-Kras mice had increased numbers of tuft cells during metaplasia and dysplasia development. In human gastric cancers, tuft cells were rarely observed, but showed positive associations with well-differentiated lesions. In mouse gastric cancer xenografts, tuft cells were restricted to dysplastic well-differentiated mucinous cysts and were lost in less differentiated cancers. Taken together, tuft cell populations increased in atrophic human gastric pathologies, metaplasia, and dysplasia, but were decreased in gastric cancers. Similar findings were observed in mouse models, suggesting that, while tuft cells are associated with precancerous pathologies, their loss is most associated with the progression to invasive cancer.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.352","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel telomere biology disease-associated gastritis identified through a whole exome sequencing-driven approach","authors":"Namrata Setia,&nbsp;Daniela del Gaudio,&nbsp;Priscilla Kandikatla,&nbsp;Kelly Arndt,&nbsp;Melissa Tjota,&nbsp;Peng Wang,&nbsp;Jeremy Segal,&nbsp;Mir Alikhan,&nbsp;John Hart","doi":"10.1002/cjp2.349","DOIUrl":"10.1002/cjp2.349","url":null,"abstract":"<p>A whole exome sequencing (WES)-driven approach to uncover the etiology of unexplained inflammatory gastritides has been underutilized by surgical pathologists. Here, we discovered the pathobiology of an unusual chronic atrophic gastritis in two unrelated patients using this approach. The gastric biopsies were notable for an unusual pattern of gastritis with persistent dense inflammation, loss of both parietal and neuroendocrine cells in the oxyntic mucosa, and sparing of the antral mucosa. The patients were found to harbor pathogenic variants in telomeropathic genes (<i>POT1</i> and <i>DCLRE1B</i>). Clonality testing for one of the patients showed evidence of evolving clonality of TCR-gene rearrangement. Both patients showed significantly decreased numbers of stem/progenitor cells by immunohistochemistry, which appears to be responsible for the development of mucosal atrophy. No such cases of unusual chronic atrophic gastritis in the setting of telomeropathy have been previously reported. The loss of stem/progenitor cells suggests that stem/progenitor cell exhaustion in the setting of telomere dysfunction is the likely mechanism for development of this unusual chronic atrophic gastritis. The results underscore the need for close monitoring of these gastric lesions, with special regard to their neoplastic potential. This combined WES-driven approach has promise to identify the cause and mechanism of other uncharacterized gastrointestinal inflammatory disorders.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.349","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138296218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-burden TP53 mutations represent frequent genetic events in CLL with an increased risk for treatment initiation","authors":"Tamás László,&nbsp;Lili Kotmayer,&nbsp;Viktória Fésüs,&nbsp;Lajos Hegyi,&nbsp;Stefánia Gróf,&nbsp;Ákos Nagy,&nbsp;Béla Kajtár,&nbsp;Alexandra Balogh,&nbsp;Júlia Weisinger,&nbsp;Tamás Masszi,&nbsp;Zsolt Nagy,&nbsp;Péter Farkas,&nbsp;Judit Demeter,&nbsp;Ildikó Istenes,&nbsp;Róbert Szász,&nbsp;Lajos Gergely,&nbsp;Adrienn Sulák,&nbsp;Zita Borbényi,&nbsp;Dóra Lévai,&nbsp;Tamás Schneider,&nbsp;Piroska Pettendi,&nbsp;Emese Bodai,&nbsp;László Szerafin,&nbsp;László Rejtő,&nbsp;Árpád Bátai,&nbsp;Mária Á Dömötör,&nbsp;Hermina Sánta,&nbsp;Márk Plander,&nbsp;Tamás Szendrei,&nbsp;Aryan Hamed,&nbsp;Zsolt Lázár,&nbsp;Zsolt Pauker,&nbsp;Gáspár Radványi,&nbsp;Adrienn Kiss,&nbsp;Gábor Körösmezey,&nbsp;János Jakucs,&nbsp;Péter J Dombi,&nbsp;Zsófia Simon,&nbsp;Zsolt Klucsik,&nbsp;Mihály Gurzó,&nbsp;Márta Tiboly,&nbsp;Tímea Vidra,&nbsp;Péter Ilonczai,&nbsp;András Bors,&nbsp;Hajnalka Andrikovics,&nbsp;Miklós Egyed,&nbsp;Tamás Székely,&nbsp;András Masszi,&nbsp;Donát Alpár,&nbsp;András Matolcsy,&nbsp;Csaba Bödör","doi":"10.1002/cjp2.351","DOIUrl":"10.1002/cjp2.351","url":null,"abstract":"<p><i>TP53</i> aberrations predict chemoresistance and represent a contraindication for the use of standard chemoimmunotherapy in chronic lymphocytic leukaemia (CLL). Recent next-generation sequencing (NGS)-based studies have identified frequent low-burden <i>TP53</i> mutations with variant allele frequencies below 10%, but the clinical impact of these low-burden <i>TP53</i> mutations is still a matter of debate. In this study, we aimed to scrutinise the subclonal architecture and clinical impact of <i>TP53</i> mutations using a sensitive, NGS-based mutation analysis in a ‘real-world’ cohort of 901 patients with CLL. In total, 225 <i>TP53</i> mutations were identified in 17.5% (158/901) of the patients; 48% of these alterations represented high-burden mutations, while 52% were low-burden <i>TP53</i> mutations. Low-burden mutations as sole alterations were identified in 39% (62/158) of all mutated cases with 82% (51/62) of these being represented by a single low-burden <i>TP53</i> mutation. Patients harbouring low-burden <i>TP53</i> mutations had significantly lower time to first treatment compared to patients with wild-type <i>TP53</i>. Our study has expanded the knowledge on the frequency, clonal architecture, and clinical impact of low-burden <i>TP53</i> mutations. By demonstrating that patients with sole low-burden <i>TP53</i> variants represent more than one-third of patients with <i>TP53</i> mutations and have an increased risk for treatment initiation, our findings strengthen the need to redefine the threshold of <i>TP53</i> variant reporting to below 10% in the routine diagnostic setting.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138177610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases","authors":"Xuesong Yang,&nbsp;Yan Wu,&nbsp;Anqiang Wang,&nbsp;Xiuli Ma,&nbsp;Kai Zhou,&nbsp;Ke Ji,&nbsp;Xin Ji,&nbsp;Ji Zhang,&nbsp;Xiaojiang Wu,&nbsp;ZhongWu Li,&nbsp;Zhaode Bu","doi":"10.1002/cjp2.343","DOIUrl":"10.1002/cjp2.343","url":null,"abstract":"<p>Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan–Meier method to find survival differences. All tumors in this study were negative for Epstein–Barr virus-encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4). About half of the tumors had a positive programmed death-ligand 1 combined positive score (CPS) and 17.3% were positive for human epidermal growth factor receptor 2 (HER2). In addition, there was a relatively high proportion of cmet expression. We also found that HAS patients with recurrent disease treated by emerging therapy had a better survival than those treated with traditional chemotherapy (<i>p</i> = 0.002, median recurrence-to-death survival: 23 months versus 6 months); HAS patients who received anti-HER2 therapy or harbored MMR deficiency had favorable prognosis. Overall, high proportions of MMR protein proficiency, positivity for AFP or SALL4, overexpression of HER2, CPS and cmet, as well as negative EBER findings, are distinctive characteristics of HAS patients. While negative EBER and MMR proficiency indicate molecular features of HAS, positivity for AFP or SALL4 could aid in the diagnosis of HAS. In addition, HAS patients could benefit from anti-HER2 therapy, immunotherapy, and anti-angiogenesis therapy.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.343","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136399897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copy number loss of KDM5D may be a predictive biomarker for ATR inhibitor treatment in male patients with pulmonary squamous cell carcinoma","authors":"Ayako Ura,&nbsp;Takuo Hayashi,&nbsp;Kazumasa Komura,&nbsp;Masaki Hosoya,&nbsp;Kazuya Takamochi,&nbsp;Eiichi Sato,&nbsp;Satomi Saito,&nbsp;Susumu Wakai,&nbsp;Takafumi Handa,&nbsp;Tsuyoshi Saito,&nbsp;Shunsuke Kato,&nbsp;Kenji Suzuki,&nbsp;Takashi Yao,&nbsp;the Tokyo Metropolitan Innovative Oncology Research Group (TMIG)","doi":"10.1002/cjp2.350","DOIUrl":"10.1002/cjp2.350","url":null,"abstract":"<p>A limited number of patients with lung squamous cell carcinoma (SCC) benefit clinically from molecular targeted drugs because of a lack of targetable driver alterations. We aimed to understand the prevalence and clinical significance of lysine-specific demethylase 5D (<i>KDM5D</i>) copy number loss in SCC and explore its potential as a predictive biomarker for ataxia-telangiectasia and Rad3-related (ATR) inhibitor treatment. We evaluated <i>KDM5D</i> copy number loss in 173 surgically resected SCCs from male patients using fluorescence <i>in situ</i> hybridization. <i>KDM5D</i> copy number loss was detected in 75 of the 173 patients (43%). Genome-wide expression profiles of the transcription start sites (TSSs) were obtained from 17 SCCs, for which the cap analysis of gene expression assay was performed, revealing that upregulated genes in tumors with the <i>KDM5D</i> copy number loss are associated with ‘cell cycle’, whereas downregulated genes in tumors with <i>KDM5D</i> copy number loss were associated with ‘immune response’. Clinicopathologically, SCCs with <i>KDM5D</i> copy number loss were associated with late pathological stage (<i>p</i> = 0.0085) and high stromal content (<i>p</i> = 0.0254). Multiplexed fluorescent immunohistochemistry showed that the number of tumor-infiltrating CD8⁺/T-bet⁺ T cells was lower in SCCs with <i>KDM5D</i> copy number loss than in wild-type tumors. In conclusion, approximately 40% of the male patients with SCC exhibited <i>KDM5D</i> copy number loss. Tumors in patients who show this distinct phenotype can be ‘cold tumors’, which are characterized by the paucity of tumor T-cell infiltration and usually do not respond to immunotherapy. Thus, they may be candidates for trials with ATR inhibitors.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136399896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering the future of 3D pathology","authors":"Jonathan TC Liu,&nbsp;Sarah SL Chow,&nbsp;Richard Colling,&nbsp;Michelle R Downes,&nbsp;Xavier Farré,&nbsp;Peter Humphrey,&nbsp;Andrew Janowczyk,&nbsp;Tuomas Mirtti,&nbsp;Clare Verrill,&nbsp;Inti Zlobec,&nbsp;Lawrence D True","doi":"10.1002/cjp2.347","DOIUrl":"10.1002/cjp2.347","url":null,"abstract":"<p>In recent years, technological advances in tissue preparation, high-throughput volumetric microscopy, and computational infrastructure have enabled rapid developments in nondestructive 3D pathology, in which high-resolution histologic datasets are obtained from thick tissue specimens, such as whole biopsies, without the need for physical sectioning onto glass slides. While 3D pathology generates massive datasets that are attractive for automated computational analysis, there is also a desire to use 3D pathology to improve the visual assessment of tissue histology. In this perspective, we discuss and provide examples of potential advantages of 3D pathology for the visual assessment of clinical specimens and the challenges of dealing with large 3D datasets (of individual or multiple specimens) that pathologists have not been trained to interpret. We discuss the need for artificial intelligence triaging algorithms and explainable analysis methods to assist pathologists or other domain experts in the interpretation of these novel, often complex, large datasets.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71428087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}