Pathology International最新文献

{"title":"Molecular pathological approach to cancer epigenomics and its clinical application.","authors":"Yae Kanai","doi":"10.1111/pin.13418","DOIUrl":"10.1111/pin.13418","url":null,"abstract":"<p><p>Careful microscopic observation of histopathological specimens, accumulation of large numbers of high-quality tissue specimens, and analysis of molecular pathology in relation to morphological features are considered to yield realistic data on the nature of multistage carcinogenesis. Since the morphological hallmark of cancer is disruption of the normal histological structure maintained through cell-cell adhesiveness and cellular polarity, attempts have been made to investigate abnormalities of the cadherin-catenin cell adhesion system in human cancer cells. It has been shown that the CDH1 tumor suppressor gene encoding E-cadherin is silenced by DNA methylation, suggesting that a \"double hit\" involving DNA methylation and loss of heterozygosity leads to carcinogenesis. Therefore, in the 1990s, we focused on epigenomic mechanisms, which until then had not received much attention. In chronic hepatitis and liver cirrhosis associated with hepatitis virus infection, DNA methylation abnormalities were found to occur frequently, being one of the earliest indications that such abnormalities are present even in precancerous tissue. Aberrant expression and splicing of DNA methyltransferases, such as DNMT1 and DNMT3B, was found to underlie the mechanism of DNA methylation alterations in various organs. The CpG island methylator phenotype in renal cell carcinoma was identified for the first time, and its therapeutic targets were identified by multilayer omics analysis. Furthermore, the DNA methylation profile of nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma was clarified in groundbreaking studies. Since then, we have developed diagnostic markers for carcinogenesis risk in NASH patients and noninvasive diagnostic markers for upper urinary tract cancer, as well as developing a new high-performance liquid chromatography-based diagnostic system for DNA methylation diagnosis. Research on the cancer epigenome has revealed that DNA methylation alterations occur from the precancerous stage as a result of exposure to carcinogenic factors such as inflammation, smoking, and viral infections, and continuously contribute to multistage carcinogenesis through aberrant expression of cancer-related genes and genomic instability. DNA methylation alterations at the precancerous stages are inherited by or strengthened in cancers themselves and determine the clinicopathological aggressiveness of cancers as well as patient outcome. DNA methylation alterations have applications as biomarkers, and are expected to contribute to diagnosis, as well as preventive and preemptive medicine.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"167-186"},"PeriodicalIF":2.5,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of cancer-induced myocardial damage in autopsy cases-A comparison of cases with and without chemotherapy.","authors":"Hitoshi Ohmori, Rina Fujiwara-Tani, Shota Nukaga, Ryoichi Nishida, Kiyomu Fujii, Shiori Mori, Ruiko Ogata, Ayaka Ikemoto, Rika Sasaki, Shingo Kishi, Yi Luo, Hiroki Kuniyasu","doi":"10.1111/pin.13411","DOIUrl":"10.1111/pin.13411","url":null,"abstract":"","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"234-238"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703041","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":"Identification of uromodulin deposition in the stroma of perinephric fibromyxoid nephrogenic adenoma by mass spectrometry.","authors":"Kaori Yoshimura, Yukinobu Ito, Mina Suzuki, Masafumi Horie, Takumi Nishiuchi, Yukako Shintani-Domoto, Kazuyoshi Shigehara, Hiroko Oshima, Masanobu Oshima, Akiteru Goto, Takayuki Nojima, Toyonori Tsuzuki, Atsushi Mizokami, Hiroko Ikeda, Daichi Maeda","doi":"10.1111/pin.13409","DOIUrl":"10.1111/pin.13409","url":null,"abstract":"<p><p>Nephrogenic adenoma (NA) is an epithelial lesion that usually occurs in the mucosa of the urinary tract. Rare cases of deep infiltrative or perinephric lesions have also been reported. Recently, NA with characteristic fibromyxoid stroma (fibromyxoid NA) has been proposed as a distinct variant. Although shedding of distal renal tubular cells due to urinary tract rupture has been postulated as the cause of NA in general, the mechanism underlying extraurinary presentation of NA and fibromyxoid stromal change in fibromyxoid NA remains unknown. In this study, we performed mass spectrometry (MS) analysis in a case of perinephric fibromyxoid NA of an 82-year-old man who underwent right nephroureterectomy for distal ureteral cancer. The patient had no prior history of urinary tract injury or radiation. Periodic acid-Schiff staining-positive eosinophilic structureless deposits in the stroma of fibromyxoid NA were microdissected and subjected to liquid chromatography/MS. The analysis revealed the presence of a substantial amount of uromodulin (Tamm-Horsfall protein). The presence of urinary content in the stroma of perinephric fibromyxoid NA suggests that urinary tract rupture and engraftment of renal tubular epithelial cells directly cause the lesion.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"187-196"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576358","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":"MicroRNA-196a-5p facilitates the onset and progression via targeting ITM2B in esophageal squamous cell carcinoma.","authors":"Dubiao Xian, Shubo Yang, Yunzhong Liu, Qingfeng Liu, Ding Huang, Yuechang Wu","doi":"10.1111/pin.13408","DOIUrl":"10.1111/pin.13408","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy affecting the digestive tract, with an increasing incidence rate worldwide. Recently, numerous studies revealed that microRNAs were associated with gene expression regulation, particularly their involvement in the regulation of tumor cells, garnering widespread attention. Here, we discovered that miR-196a-5p was significantly upregulated in both ESCC tissues and cells, which was correlated with an unfavorable prognosis. Series functional in vitro investigations have confirmed that silencing miR-196a-5p obviously restrained the ESCC cells malignant phenotypes and promoted apoptosis. Bioinformatics analysis and rescue experiments revealed that miR-196a-5p directly targeted ITM2B, exerting influence on the development of ESCC cells through negative regulation of ITM2B expression. Xenograft mouse models were established for conducting in vivo experiments, providing further confirmation of the regulatory mechanism and biological significance of the miR-196a-5p/ITM2B axis in ESCC. Our research demonstrated miR-196a-5p promoted ESCC malignant progression by interacting with ITM2B, thereby providing novel clues and potential targets for the new diagnosis and thereby of ESCC.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"129-138"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576360","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":"Erianin inhibits tumor growth by promoting ferroptosis and inhibiting invasion in hepatocellular carcinoma through the JAK2/STAT3/SLC7A11 pathway.","authors":"Liyan Chen, Rongrong Sun, Kun Fang","doi":"10.1111/pin.13403","DOIUrl":"10.1111/pin.13403","url":null,"abstract":"<p><p>Iron has been found to be involved in the tumor cell proliferation process, which can lead to the increased sensitivity of cancer cells to ferroptosis. Since erianin is associated with oxidative stress in hepatocellular carcinoma (HCC), we hypothesized that the therapeutic effect and mechanism of erianin on HCC is related to ferroptosis. HCC cells were stimulated with increase of erianin concentrations for 24 h, and the survival rates of Huh-7 and HepG2 cells gradually decreased. After intervention with different doses of erianin, cell proliferation, clone number, and invasion were prominently decreased, apoptosis ratio was increased. Moreover, Nec-1, CQ, and Z-VAD had no effect on the cell viability induced by erianin, while the combination of ferroptosis inhibitors (deferoxamine mesylate, ferrostatin-1, and liproxstatin-1) and erianin prominently increased cell survival rate. Erianin pretreatment induced ferroptosis by enhancing reactive oxygen species, MDA, and Fe²⁺ levels, and reducing GSH levels. Erianin activated JAK2/STAT3 pathway and inhibited SLC7A11 and GPX4 expression, thereby inducing ferroptosis. Besides, tumor growth was significantly inhibited in the erianin-treated mice, and there was no obvious toxicity in the mice. Erianin reduced proliferation and invasion of HCC cells by inducing ferroptosis by blocking the JAK2/STAT3/SLC7A11 pathway, thereby impeding tumor growth.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"119-128"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491771","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":"Carcinogenesis caused by transcription-coupled DNA damage through GANP and other components of the TREX-2 complex.","authors":"Yasuhiro Sakai, Kazuhiko Kuwahara","doi":"10.1111/pin.13415","DOIUrl":"10.1111/pin.13415","url":null,"abstract":"<p><p>Perturbation of genes is important for somatic hypermutation to increase antibody affinity during B-cell immunity; however, it may also promote carcinogenesis. Previous studies have revealed that transcription is an important process that can induce DNA damage and genomic instability. Transciption-export-2 (TREX-2) complex, which regulates messenger RNA (mRNA) nuclear export, has been studied in the budding yeast Saccharomyces cerevisiae; however, recent studies have started investigating the molecular function of the mammalian TREX-2 complex. The central molecule in the TREX-2 complex, that is, germinal center-associated nuclear protein (GANP), is closely associated with antibody affinity maturation as well as cancer etiology. In this review, we focus on carcinogenesis, lymphomagenesis, and teratomagenesis caused by transcription-coupled DNA damage through GANP and other components of the TREX-2 complex. We review the basic machinery of mRNA nuclear export and transcription-coupled DNA damage. We then briefly describe the immunological relationship between GANP and the affinity maturation of antibodies. Finally, we illustrate that the aberrant expression of the components of the TREX-2 complex, especially GANP, is associated with the etiology of various solid tumors, lymphomas, and testicular teratoma. These components serve as reliable predictors of cancer prognosis and response to chemotherapy.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"103-118"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139973024","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":"Pseudoimmunofluorescent immunohistochemistry image analysis of phosphorylated signaling proteins in human esophageal squamous cell carcinoma tissue.","authors":"Mari Nishio, Shuichi Tsukamoto, Takayuki Kodama, Manabu Shigeoka, Yu-Ichiro Koma, Hiroshi Yokozaki","doi":"10.1111/pin.13407","DOIUrl":"10.1111/pin.13407","url":null,"abstract":"<p><p>Immunohistochemistry is primarily employed to visualize the localization of specific molecules in tissue samples. However, there is an increasing need for software-assisted quantitative assessment. In the present study, we performed inverted blue channel-based pseudoimmunofluorescence image analysis using original immunohistochemistry images. In human esophageal squamous cell carcinoma tissues, various humoral factors promote the phosphorylation of signaling proteins, including protein kinase B (Akt) and/or extracellular signal-regulated kinase 1/2 (ERK1/2), leading to tumor progression. Our method demonstrated applicability in the analysis of localized signaling proteins in histological sections. Relatively high phosphorylated Akt (p-Akt) intensity was observed in the cancer-stroma adjacent (Adj) and noncancerous regions of the superficial layer (SL). Furthermore, localized phosphorylated ERK1/2 (Thr202/Tyr204) was observed in the Adj of the SL and invasive front, distinct from the pattern of p-Akt (Ser473) and p-Akt (Thr308). In conclusion, pseudoimmunofluorescent immunohistochemistry image analysis is useful for the quantitative assessment and objective interpretation of localized signaling proteins in esophageal squamous cell carcinoma. The method can also be applied to analyze various immunohistochemistry images from diverse tissues.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"139-145"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139522473","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":"Enterocolic granulomatous phlebitis associated with epidermal growth factor-containing fibulin-like extracellular matrix protein 1 deposition and focal amyloid properties: A case report.","authors":"Shojiro Ichimata, Akane Aikawa, Naonori Sugishita, Nagaaki Katoh, Fuyuki Kametani, Hibiki Tagawa, Yusuke Handa, Masahide Yazaki, Yoshiki Sekijima, Takashi Ehara, Naoki Nishida, Shin Ishizawa","doi":"10.1111/pin.13405","DOIUrl":"10.1111/pin.13405","url":null,"abstract":"<p><p>A woman in her 60s with rheumatoid arthritis was admitted with fever and abdominal pain. Laparoscopic examination with the differential diagnosis of peritoneal neoplasm and infection revealed granulomatous phlebitis in the resected greater omentum. Amorphous eosinophilic deposits observed in the resected tissue exhibited focal, weak positivity for Congo red but were strongly positive for thioflavin S, confirming their focal amyloid properties. Marked degeneration of elastic fibers was also evident. Electron microscopy revealed deposits around the affected elastic fibers. Immunohistochemistry revealed the deposition of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) along with T-cell-predominant lymphocytic inflammation. The definitive diagnosis was granulomatous enterocolic lymphocytic phlebitis (ELP) associated with EFEMP1 deposition exhibiting focal amyloid properties (EFEMP1/AEFEMP1), supported by proteomics analysis. This type of vasculitis is similar to amyloid-β-related angiitis of the central nervous system. Thus, we speculate that granulomatous ELP also results from an immune response that recognizes EFEMP1/AEFEMP1 deposits as foreign material and attempts to remove them. Confirmation of EFEMP1/AEFEMP1 deposition with Congo red staining is challenging, particularly in the presence of inflammation, and warrants comprehensive evaluation.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"146-153"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491768","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":"Alteration of small intestinal occludin and ZO-1 expession in liver cirrhosis.","authors":"Theodoros Voulgaris, Dina Tiniakos, Dimitrios Karagiannakis, Despoina Myoteri, Despoina Karandrea, Spilios Manolakopoulos, George Papatheodoridis, Jiannis Vlachogiannakos","doi":"10.1111/pin.13406","DOIUrl":"10.1111/pin.13406","url":null,"abstract":"","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"154-156"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513313","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":"Late relapsing testicle cancer identified with isochromosome 12p (i12p) fluorescence in situ hybridization (FISH) analysis.","authors":"Teruki Isobe, Noriyasu Kawai, Maria Aoki, Toshiharu Morikawa, Masakazu Gonda, Nami Tomiyama, Takashi Nagai, Keitaro Iida, Toshiki Etani, Taku Naiki, Toyonori Tsuzuki, Takahiro Yasui","doi":"10.1111/pin.13414","DOIUrl":"10.1111/pin.13414","url":null,"abstract":"","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":" ","pages":"160-162"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990845","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}