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A Novel Tight Junction-Nuclear Receptor Signaling Pathway Regulating Cancer Progression. 一种调节癌症进展的新型紧密连接-核受体信号通路。
IF 2.5 4区 医学
Pathology International Pub Date : 2025-07-25 DOI: 10.1111/pin.70040
Kotaro Sugimoto, Hideki Chiba
{"title":"A Novel Tight Junction-Nuclear Receptor Signaling Pathway Regulating Cancer Progression.","authors":"Kotaro Sugimoto, Hideki Chiba","doi":"10.1111/pin.70040","DOIUrl":"https://doi.org/10.1111/pin.70040","url":null,"abstract":"<p><p>Nuclear receptors (NRs) are lipid ligand-binding transcription factors, with 48 members having been identified in humans to date. They are involved in diverse physiological processes, including development and homeostasis, and are also implicated in the pathogenesis of various diseases, most notably cancer. While NR activity is primarily regulated by specific ligand binding, posttranslational modifications, particularly phosphorylation, also play a critical role in modulating their function. Recently, we identified a novel signaling pathway linking claudins (CLDNs), cell-cell adhesion proteins, to NRs. CLDN-mediated cell-cell adhesion activates Src family kinases (SFKs), leading to serine phosphorylation of several NRs. This newly-discovered CLDN-NR pathway contributes to epithelial differentiation in stem cells and promotes cancer progression. In this review, we discuss the biological significance and underlying mechanisms of this, tracing the development of our research.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Does the Size of Perineural Cancer Invasion on Prostate Needle Core Biopsy Have a Clinical Impact? 前列腺穿刺活检对神经周围癌浸润的大小有临床影响吗？
IF 2.5 4区 医学
Pathology International Pub Date : 2025-07-24 DOI: 10.1111/pin.70039
Hangchuan Shi, Ying Wang, Hiroshi Miyamoto
{"title":"Does the Size of Perineural Cancer Invasion on Prostate Needle Core Biopsy Have a Clinical Impact?","authors":"Hangchuan Shi, Ying Wang, Hiroshi Miyamoto","doi":"10.1111/pin.70039","DOIUrl":"https://doi.org/10.1111/pin.70039","url":null,"abstract":"","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinicopathological Significance of Spread Through Air Spaces in Lung Cancer. 肺癌经气道扩散的临床病理意义。
IF 2.5 4区 医学
Pathology International Pub Date : 2025-07-22 DOI: 10.1111/pin.70037
Emi Ibuki, Chihiro Yoshida, Kyuichi Kadota
{"title":"Clinicopathological Significance of Spread Through Air Spaces in Lung Cancer.","authors":"Emi Ibuki, Chihiro Yoshida, Kyuichi Kadota","doi":"10.1111/pin.70037","DOIUrl":"https://doi.org/10.1111/pin.70037","url":null,"abstract":"<p><p>Although it has been known for over 40 years that lung cancer can progress by spreading through alveolar spaces, the WHO formally published the term \"spread through air spaces\" (STAS) only 10 years ago, in 2015. Numerous studies have proven that STAS is a poor prognostic factor in all histological types of lung cancer and affects surgical procedure selection and stage classification. While it is clear that STAS should be reported in the routine diagnosis of lung cancer, diagnosis can sometimes be challenging, and pathologists need to be aware of the diagnostic and exclusion criteria. Clinicians also need to recognize the importance of STAS and cooperate in improving diagnosis using frozen sections, which has become a topic of discussion in recent years. In this review, we summarize the current status of research on STAS from various perspectives, including clinical, morphological, genetic, molecular, and tumor immune microenvironmental properties, and discuss future prospects.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Significance of Cytoplasmic STAT6 Positivity and High p53/p16 Expression as a Novel Predictor of Histological/Clinical Malignancy in NAB2::STAT6 Fusion-Positive Orbital Solitary Fibrous Tumors. 细胞质STAT6阳性和p53/p16高表达作为NAB2::STAT6融合阳性眼眶孤立性纤维性肿瘤组织学/临床恶性肿瘤的新预测因子的意义
IF 2.5 4区 医学
Pathology International Pub Date : 2025-07-17 DOI: 10.1111/pin.70036
Satoshi Adachi, Akihide Kondo, Ikuko Ogino, Mario Suzuki, Yuzaburo Shimizu, Osamu Akiyama, Takuo Hayashi, Arata Tomiyama
{"title":"The Significance of Cytoplasmic STAT6 Positivity and High p53/p16 Expression as a Novel Predictor of Histological/Clinical Malignancy in NAB2::STAT6 Fusion-Positive Orbital Solitary Fibrous Tumors.","authors":"Satoshi Adachi, Akihide Kondo, Ikuko Ogino, Mario Suzuki, Yuzaburo Shimizu, Osamu Akiyama, Takuo Hayashi, Arata Tomiyama","doi":"10.1111/pin.70036","DOIUrl":"https://doi.org/10.1111/pin.70036","url":null,"abstract":"<p><p>Orbital solitary fibrous tumor (SFT) is an extremely rare variant of systemic SFTs. However, the relationship between the biological/clinical characteristics, histological malignancies, and known oncogenes of systemic SFTs has not yet been elucidated. Therefore, we investigated these features and explored the prognostic factors of orbital SFTs by analyzing a series of orbital SFT cases. Six orbital SFT and one meningeal SFT were analyzed for comparison. NAB2::STAT6 variants were identified in five of the six orbital SFTs cases and one meningeal SFT case. There was no correlation between the exon composition of NAB2::STAT6 variants and the time of relapse after surgery or histological malignancy. Nuclear STAT6 staining by immunohistochemistry was observed in all cases, whereas cytosolic STAT6 staining was confirmed in three orbital SFT cases. The presence of histological malignancies and positive cytosolic STAT6 staining were mutually exclusive. The diffuse strong expressions of p53 and p16 were confirmed only in a case with the worst clinical course. No TERT promoter mutations were observed in any of these cases. Our study suggests that positivity of cytosolic STAT6 staining and high p53/p16 expression may be a predictor of histological/clinical malignancy in orbital SFT. Further evidence is necessary to confirm our results.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Trends in Pathological Autopsy in Japan From 1958 to 2023. 1958 - 2023年日本病理尸检趋势
IF 2.5 4区 医学
Pathology International Pub Date : 2025-07-16 DOI: 10.1111/pin.70038
Hiroshi Uozaki, Yoshinao Kikuchi, Masato Watanabe
{"title":"Trends in Pathological Autopsy in Japan From 1958 to 2023.","authors":"Hiroshi Uozaki, Yoshinao Kikuchi, Masato Watanabe","doi":"10.1111/pin.70038","DOIUrl":"https://doi.org/10.1111/pin.70038","url":null,"abstract":"<p><p>Pathological autopsies are essential for medical education and medical progress, yet their numbers have been declining globally. Annual of the Pathological Autopsy Cases in Japan (APAC-J), established in 1958, is a comprehensive nationwide database of autopsies performed in Japan. This study analyzed APAC-J data from 1958 to 2023, encompassing over 1.49 million cases. The number of autopsies peaked at 40,680 in 1985 but declined significantly to 10,020 in 2019, and further to 6,557 in 2022 largely due to the COVID-19 pandemic. Autopsy rates declined after the medical school conflicts in the late 1960s, with temporary increases following the introduction of board certification for pathologists. The number of data-reporting facilities rose to 934 by 2019. Since 2000, the proportion of brain dissections has slightly increased, while limited autopsies have decreased (24% and 3.9%, respectively, in 2023). The male-to-female ratio is over 2.0, and average ages of autopsy cases remain over 10 years younger than Japanese life expectancy. Autopsy rates were higher among individuals from childhood to middle age. This study demonstrates that social dynamics and healthcare system reforms have influenced autopsy practices. Interpretation of autopsy case groups must consider demographic characteristics and shifts in autopsy implementation over time.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Uterine Mesenchymal Neoplasm With a Novel CDC42::PLAG1 Fusion. 子宫间质肿瘤与新型CDC42::PLAG1融合。
IF 2.5 4区 医学
Pathology International Pub Date : 2025-07-03 DOI: 10.1111/pin.70035
Pranav Dorwal, Diarmid Foulis, Jing Jing Li, Michael Burling, Lyndal Anderson
{"title":"Uterine Mesenchymal Neoplasm With a Novel CDC42::PLAG1 Fusion.","authors":"Pranav Dorwal, Diarmid Foulis, Jing Jing Li, Michael Burling, Lyndal Anderson","doi":"10.1111/pin.70035","DOIUrl":"https://doi.org/10.1111/pin.70035","url":null,"abstract":"","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gastric Neuroendocrine Tumor With Pancreatic Acinar Cell Differentiation in the Background of Atrophic Gastritis: A Possible Variant of Type 1 ECL-Cell NET-A Case Report. 萎缩性胃炎背景下胃神经内分泌肿瘤伴胰腺腺泡细胞分化：1型ecl细胞NET-A可能的变异病例报告。
IF 2.5 4区 医学
Pathology International Pub Date : 2025-07-01 Epub Date: 2025-05-06 DOI: 10.1111/pin.70022
Tomoko Norose, Nobuyuki Ohike, Misato Tsukada, Yoshiya Sugiura, Hirotaka Koizumi, Yusuke Nakamoto, Keisuke Tateishi, Shinya Mikami, Junki Koike
{"title":"Gastric Neuroendocrine Tumor With Pancreatic Acinar Cell Differentiation in the Background of Atrophic Gastritis: A Possible Variant of Type 1 ECL-Cell NET-A Case Report.","authors":"Tomoko Norose, Nobuyuki Ohike, Misato Tsukada, Yoshiya Sugiura, Hirotaka Koizumi, Yusuke Nakamoto, Keisuke Tateishi, Shinya Mikami, Junki Koike","doi":"10.1111/pin.70022","DOIUrl":"10.1111/pin.70022","url":null,"abstract":"<p><p>A gastric neuroendocrine tumor (NET) with pancreatic acinar cell differentiation is extremely rare. We report the case of an 87-year-old woman with a submucosal tumor in the gastric body on a background of atrophic gastritis. She also had Sjögren's syndrome. Initially 17.8 × 6.5 mm, the tumor enlarged over 10 years, leading to wedge resection. The resected mass (45 × 40 × 30 mm) was solid with a pale yellow to gray-white cut surface. Histologically, it showed trabecular or solid nests of epithelial cells with round nuclei and eosinophilic cytoplasm. Immunohistochemistry showed positivity for CKAE1/3, VMAT2, neuroendocrine markers, and pancreatic acinar markers. Ki-67 index was 11.2%. The tumor co-expressed PDX1 and ARX and showed loss of menin and ATRX. These findings support a diagnosis of gastric ECL-cell NET G2 arising in autoimmune gastritis, with secondary pancreatic acinar differentiation. This tumor may represent a variant of type 1 gastric NET.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"359-365"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SMARCB1-Deficient Pulmonary Mesenchymal Tumor Without Malignant Histological Features. 无恶性组织学特征的缺乏smarcb1的肺间充质肿瘤。
IF 2.5 4区 医学
Pathology International Pub Date : 2025-07-01 Epub Date: 2025-05-16 DOI: 10.1111/pin.70025
Nozomi Nakajima, Kohei Fukuoka, Seshiru Nakazawa, Yoichi Ohtaki, Nozomi Matsumura, Ayako Yamazaki, Hideaki Yokoo, Akihiko Yoshida, Sumihito Nobusawa
{"title":"SMARCB1-Deficient Pulmonary Mesenchymal Tumor Without Malignant Histological Features.","authors":"Nozomi Nakajima, Kohei Fukuoka, Seshiru Nakazawa, Yoichi Ohtaki, Nozomi Matsumura, Ayako Yamazaki, Hideaki Yokoo, Akihiko Yoshida, Sumihito Nobusawa","doi":"10.1111/pin.70025","DOIUrl":"10.1111/pin.70025","url":null,"abstract":"<p><p>Complete loss of nuclear SMARCB1 expression was originally described as a hallmark of malignant rhabdoid tumors, typically occurring in the kidney, soft tissue, and central nervous system (CNS). Generally, SMARCB1 deficiency is associated with malignant histopathological appearance, except for some rare tumors. Herein, we present a case of hitherto undescribed SMARCB1-deficient pulmonary mesenchymal tumor without rhabdoid features or malignant histopathology involving a 62-year-old male patient. Histologically, the tumor demonstrated a moderately cellular proliferation of monomorphic spindle cells arranged in short fascicles or a storiform pattern with intervening collagenous stroma. The mitotic activity was lower than that of typical SMARCB1-deficient tumors, and rhabdoid features and necrosis were absent. Nuclear SMARCB1 expression was lost, and a part of SMARCB1 was revealed to be homozygously deleted. DNA methylation analysis demonstrated that this case was not clustered with other well-known SMARCB1-deficient tumors.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"366-372"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinicopathological Characterization of Squamous Cell Lung Carcinoma Adjacent to Emphysema. 肺鳞状细胞癌伴肺气肿的临床病理特征。
IF 2.5 4区 医学
Pathology International Pub Date : 2025-07-01 Epub Date: 2025-05-21 DOI: 10.1111/pin.70023
Tetsuya Sakai, Hibiki Udagawa, Hiroki Izumi, Shigeki Umemura, Yoshitaka Zenke, Shingo Matsumoto, Kiyotaka Yoh, Naito Tomoyuki, Nakai Tokiko, Tetsuro Taki, Naoya Sakamoto, Shingo Sakashita, Motohiro Kojima, Masahiro Tsuboi, Koichi Goto, Genichiro Ishii
{"title":"Clinicopathological Characterization of Squamous Cell Lung Carcinoma Adjacent to Emphysema.","authors":"Tetsuya Sakai, Hibiki Udagawa, Hiroki Izumi, Shigeki Umemura, Yoshitaka Zenke, Shingo Matsumoto, Kiyotaka Yoh, Naito Tomoyuki, Nakai Tokiko, Tetsuro Taki, Naoya Sakamoto, Shingo Sakashita, Motohiro Kojima, Masahiro Tsuboi, Koichi Goto, Genichiro Ishii","doi":"10.1111/pin.70023","DOIUrl":"10.1111/pin.70023","url":null,"abstract":"<p><p>The study investigated the clinicopathological features and characteristic immune tumor microenvironment (TME) of lung squamous cell carcinoma (SqCC) adjacent to emphysematous lesions. 184 consecutive patients with peripheral-type SqCC who had undergone complete surgical resection were enrolled. The clinicopathological differences between emphysema-adjacent SqCC (EA-SqCC) and non-emphysema-adjacent SqCC (non-EA-SqCC) were examined. The immune TME, including tumor-infiltrating lymphocytes (TILs) and PD-L1 expression, was also analyzed. EA-SqCC was detected in 132 (71.7%) of the 184 patients. Patients with EA-SqCC had shorter recurrence-free survival (RFS) [median 58.2 months vs. not Reached (NR); hazard ratio (HR) 0.47; 95% CI 0.25-0.81, p < 0.01] and tended to have shorter overall survival (NR vs. NR; HR 0.47; 95% CI 0.27-1.03, p = 0.07) compared to patients with non-EA-SqCC. Evaluation of TILs in the cancer stroma showed the number of Foxp3+ TILs in the EA-SqCC group was significantly higher than that in the non-EA-SqCC group (median number 58 vs. 43, p < 0.01). However, there were no significant differences in the number of CD8 + T cells and the PD-L1 expression between the two groups. Immunosuppressive microenvironment is a characteristic feature of EA-SqCC, which may contribute to the poor prognosis of this disease.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"329-339"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DNA Degradation in FFPE Tissue Samples Caused by Air Transport: An Experimental Evaluation of Radiation Exposure. 航空运输引起的FFPE组织样品中的DNA降解：辐射暴露的实验评估。
IF 2.5 4区 医学
Pathology International Pub Date : 2025-07-01 Epub Date: 2025-06-03 DOI: 10.1111/pin.70027
Rio Yamaguchi, Takahiro Yamane, Masahiro Oita, Hirofumi Inoue, Mizuki Morita
{"title":"DNA Degradation in FFPE Tissue Samples Caused by Air Transport: An Experimental Evaluation of Radiation Exposure.","authors":"Rio Yamaguchi, Takahiro Yamane, Masahiro Oita, Hirofumi Inoue, Mizuki Morita","doi":"10.1111/pin.70027","DOIUrl":"10.1111/pin.70027","url":null,"abstract":"<p><p>Air transport of FFPE cancer tissue samples led to increased DNA fragmentation, primarily due to radiation exposure rather than temperature changes or freeze-thaw cycles. While overall degradation was minor, critical samples requiring high nucleic acid integrity may benefit from local testing or research. Avoiding air transport could help mitigate potential risks and ensure reliable results.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"382-385"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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