Pathology, research and practice最新文献

{"title":"Emerging molecular phenotypes and potential therapeutic targets in esophageal and gastric adenocarcinoma unearthed by whole genome and transcriptome analyses","authors":"Annika Windon ,&nbsp;Majd Al Assaad ,&nbsp;Kevin Hadi ,&nbsp;Nicole Mendelson ,&nbsp;Erika Hissong ,&nbsp;Aditya Deshpande ,&nbsp;Marvel Tranquille ,&nbsp;Justin Mclee ,&nbsp;Max F. Levine ,&nbsp;Minal Patel ,&nbsp;Juan S. Medina-Martínez ,&nbsp;Kenrry Chiu ,&nbsp;Jyothi Manohar ,&nbsp;Michael Sigouros ,&nbsp;Allyson J. Ocean ,&nbsp;Andrea Sboner ,&nbsp;José Jessurun ,&nbsp;Olivier Elemento ,&nbsp;Manish Shah ,&nbsp;Juan Miguel Mosquera","doi":"10.1016/j.prp.2024.155788","DOIUrl":"10.1016/j.prp.2024.155788","url":null,"abstract":"<div><h3>Background</h3><div>Adenocarcinoma of the esophagus and stomach demands a deeper molecular understanding to advance treatment strategies and improve patient outcomes. Here, we profiled the genome and transcriptome landscape of these cancers, explored molecular characteristics that are undetectable by other sequencing platforms, and analyzed their potential clinical ramifications.</div></div><div><h3>Methods</h3><div>Our study employed state-of-the-art integrative analyses of whole genome and transcriptome sequencing on 51 matched tumor and germline samples from 46 patients. Mutations and rearrangements in clinically relevant cancer genes were investigated and correlated with OncoKB, a knowledge-based precision oncology database, to identify treatment implications. Genome-wide signatures and manually curated molecular profiles were also determined.</div></div><div><h3>Results</h3><div>The analyses revealed 90 targetable oncogenic mutations and fusions in 63 % of the patients, including novel <em>NTRK, NRG1, ALK,</em> and <em>MET</em> fusions, and structural variants in cancer genes like <em>RAD51B</em>. Also, molecular signatures associated with mismatch repair and homologous recombination deficiency were elucidated. Notably, we identified <em>CDK12</em>-type genomic instability associated with <em>CDK12</em> fusions.</div></div><div><h3>Conclusions</h3><div>Our findings support the potential of whole genome and transcriptome sequencing analyses as a comprehensive approach to identify treatment targets in adenocarcinoma of the stomach and the esophagus, and their application in precision oncology.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155788"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872719","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":"Exosome-mediated delivery of CRISPR-Cas9: A revolutionary approach to cancer gene editing","authors":"Ashok Kumar Balaraman ,&nbsp;M.Arockia Babu ,&nbsp;Ehssan Moglad ,&nbsp;Viralkumar Mandaliya ,&nbsp;M.M. Rekha ,&nbsp;Sofia Gupta ,&nbsp;G.V. Siva Prasad ,&nbsp;Mukesh Kumari ,&nbsp;Ashish Singh Chauhan ,&nbsp;Haider Ali ,&nbsp;Kavita Goyal","doi":"10.1016/j.prp.2024.155785","DOIUrl":"10.1016/j.prp.2024.155785","url":null,"abstract":"<div><div>Several molecular strategies based on targeted gene delivery systems have been developed in recent years; however, the CRISPR-Cas9 technology introduced a new era of targeted gene editing, precisely modifying oncogenes, tumor suppressor genes, and other regulatory genes involved in carcinogenesis. However, efficiently and safely delivering CRISPR-Cas9 to cancer cells across the cell membrane and the nucleus is still challenging. Using viral vectors and nanoparticles presents issues of immunogenicity, off-target effects, and low targeting affinity. Naturally, extracellular vesicles called exosomes have garnered the most attention as delivery vehicles in oncology-related CRISPR-Cas9 calls due to their biocompatibility, loading capacity, and inherent targeting features. The following review discusses the current progress in using exosomes to deliver CRISPR-Cas9 components, the approaches to load the CRISPR components into exosomes, and the modification of exosomes to increase stability and tumor-targeted delivery. We discuss the latest strategies in targeting recently accomplished in the exosome field, including modifying the surface of exosomes to enhance their internalization by cancer cells, as well as the measures taken to overcome the impacts of TME on delivery efficiency. Focusing on in vitro and in vivo experimentation, this review shows that exosome-mediated CRISPR-Cas9 can potentially treat cancer types, including pancreatic, lymphoma, and leukemia, for given gene targets. This paper compares exosome-mediated delivery and conventional vectors regarding safety, immune response, and targeting ability. Last but not least, we present the major drawbacks and potential development of the seemingly promising field of exosome engineering in gene editing, with references to CRISPR technologies and applications that may help make the target exosomes therapeutic in oncology.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155785"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872722","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":"The effect of prolonged cold ischemia time on breast cancer biomarker expression after neoadjuvant chemotherapy","authors":"Ida Ghlichloo,&nbsp;Wangpan Jackson Shi,&nbsp;Oluwole Fadare","doi":"10.1016/j.prp.2024.155781","DOIUrl":"10.1016/j.prp.2024.155781","url":null,"abstract":"<div><div>Prolonged cold ischemia time (CIT) and neoadjuvant chemotherapy (NACT) can each independently impact the expression of breast cancer-related biomarkers, but their combined effects are not well studied. Herein, we assessed whether prolonged CIT has a higher modulatory effect on post-NACT biomarker expression in breast cancer specimens than in otherwise similar but non-NACT specimens. Our study cohort included 334 biopsy/resection breast cancer specimen pairs in which immunohistochemistry (IHC for estrogen receptor [ER], progesterone receptor [PR], HER2) and HER2 FISH had been performed on both specimens. These included 209 pairs with a post-NACT resection (NACT[+]), and 125 pairs unassociated with NACT (NACT[-]). Each group was subclassified into prolonged CIT (&gt;1 hr; CITp) and non-prolonged CIT (≤1 hr, CITnp). NACT[+]/CITp (n = 125) and NACT[-]/CITp (n = 84) subgroups showed no statistically significant differences regarding the frequency of biopsy-to-resection change in the final result [i.e. positive versus negative] for any of the 4 biomarkers. Similarly, the NACT[+]/CITp and NACT[+]/CITnp subgroups showed no significant differences regarding the percentage of cases with any biopsy-to-resection change in final result for ER, HER2 (IHC) and HER2 (FISH). For PR, a biopsy-to-resection change in status was more commonly observed in CITnp (44.1 %) as compared to the CITp (19.2 %) subgroup (p = 0.02). In summary, we found no conclusive evidence that prolonged CIT has a more significant modulatory effect on biomarker expression in post-NACT breast cancer resection specimens than their otherwise comparable (i.e. NACT[-], CITp) counterparts regarding the final test result, which suggests that post-NACT specimens do not require more stringent CIT-related handling requirements than NACT[-] specimens.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155781"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877847","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":"Integrative analysis disclosing UQCRC1 as a potential prognostic and immunological biomarker of lung adenocarcinoma","authors":"Lv Ling ,&nbsp;Cong Peng ,&nbsp;Sheng Lin ,&nbsp;Yuanhang Chen ,&nbsp;Min Deng ,&nbsp;Huisi Qiu ,&nbsp;Yuanfeng Huang","doi":"10.1016/j.prp.2025.155816","DOIUrl":"10.1016/j.prp.2025.155816","url":null,"abstract":"<div><div>Lung cancer is one of the most malignant cancers in the world. Approximately 40 % of lung cancer cases are lung adenocarcinoma (LUAD). Exploring new biomarkers was an urgent need for treatments of LUAD. Here, we aimed to perform a pan-cancer analysis of ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) and verify it in LUAD. Compared to normal samples, we observed that UQCRC1 was significantly enhanced in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), LUAD, liver hepatocellular carcinoma (LIHC), and several other cancers. In terms of overall survival, UQCRC1 was positively associated with poor prognosis of LUAD and skin cutaneous melanoma (SKCM). Almost more than 8 % deeply deleted frequency of UQCRC1 was showed in lymphoid neoplasm diffuse large B-cell lymphoma (DLBC). In LUAD, SKCM, and a few cancers, UQCRC1 was negatively correlated with the infiltration of B cells and cancer-associated fibroblasts. As regards further mechanism analysis, we found that UQCRC1 modulated cancer progression via mitochondrial related metabolism and oxidative phosphorylation. Taking advantage of the Kras-driven spontaneous LUAD mice model, online single-cell data, and clinical tissues, we particularly confirmed that UQCRC1 was highly expressed in LUAD and acted as a prognostic marker for LUAD. These findings implied that UQCRC1 played an important role in cancers, especially in LUAD.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155816"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971869","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":"Renal cell carcinoma with ALK-TPM3 gene fusion and ALK amplification: A case report and literature review","authors":"Xinzhuo Tu ,&nbsp;Min Zhu ,&nbsp;Qingyue Liu ,&nbsp;Xu Liu ,&nbsp;Yayun Qi ,&nbsp;Yuanlin Zhang ,&nbsp;Haili Li ,&nbsp;Tianzhu Tao ,&nbsp;Jinjin Chang ,&nbsp;Jianping Zhu ,&nbsp;Dawei Mu ,&nbsp;Li Ren ,&nbsp;Dengfeng Cao ,&nbsp;Teng Li","doi":"10.1016/j.prp.2025.155814","DOIUrl":"10.1016/j.prp.2025.155814","url":null,"abstract":"<div><h3>Background</h3><div>Anaplastic lymphoma kinase (ALK)–rearranged renal cell carcinoma (ALK-RCC) is a rare molecularly defined tumor entity included in the fifth edition of the World Health Organization Classification of Tumors. It is characterized by rearrangement of the ALK gene with various fusion partner genes, which most commonly results in oncogenic fusion proteins leading to ALK activation.</div></div><div><h3>Case Presentation</h3><div>A 30-year-old Chinese man underwent partial nephrectomy for a left renal tumor measuring 5 cm in diameter. Histologically, the tumor is pleomorphic and arranged in papillary, tubular, and solid patterns. At high magnification, abundant eosinophilic cytoplasm, obvious cytoplasmic vacuolation, and displaced nuclei were observed. Immunohistochemistry revealed diffuse positivity for PAX8,CK7,CAIX, and ALK(D5F3). Fluorescence in situ hybridization (FISH) showed ALK amplification and break-apart in tumor cells. ALK-TPM3 gene fusion and ALK amplification were detected by next-generation sequencing.</div></div><div><h3>Conclusion</h3><div>We report the first case of ALK-RCC with concurrent ALK amplification and fusion. This article presents the clinical data, morphology, immunohistochemistry, and molecular characteristics of this case, with the aim of enhancing the clinical and pathological understanding of ALK-RCC among clinicians and pathologists.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155814"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009706","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":"Spatial transcriptome analysis of lung squamous cell carcinoma arising from interstitial pneumonia provides insights into tumor heterogeneity","authors":"Koto Ukon ,&nbsp;Satoshi Nojima ,&nbsp;Daisuke Motooka ,&nbsp;Tsuyoshi Takashima ,&nbsp;Masaharu Kohara ,&nbsp;Hiroki Kiyokawa ,&nbsp;Kenji Kimura ,&nbsp;Eriko Fukui ,&nbsp;Shinichiro Tahara ,&nbsp;Kansuke Kido ,&nbsp;Takahiro Matsui ,&nbsp;Yasushi Shintani ,&nbsp;Daisuke Okuzaki ,&nbsp;Eiichi Morii","doi":"10.1016/j.prp.2024.155805","DOIUrl":"10.1016/j.prp.2024.155805","url":null,"abstract":"<div><div>Interstitial pneumonia (IP) is a refractory disease that causes severe inflammation and fibrosis in the interstitium of the lungs, often resulting in the development of lung cancer (LC) during treatment. Previous studies have demonstrated that the prognosis of LC complicated by IP is inferior to that of LC without IP. It is therefore of the utmost importance to gain a deeper understanding of the heterogeneity of such tumors. In the present study, we conducted spatial transcriptome analysis of squamous cell carcinoma arising from IP. The results suggested involvement of the glucocorticoid receptor pathway in treatment resistance. Immunostaining of squamous cell carcinoma specimens from patients with IP demonstrated that the tumors expressed <em>NR3C1</em> to varying degrees. Furthermore, higher <em>NR3C1</em> expression levels were associated with a significantly increased risk of recurrence. Our results point to a novel subtype of lung squamous cell carcinoma. Further analysis of the molecular mechanisms associated with this subtype may facilitate the development of novel diagnostic criteria and therapeutic approaches.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155805"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932433","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":"Signature of collagen alpha-1(x) gene expression in human cancers and their therapeutic implications","authors":"Akshaya Nagarajan ,&nbsp;Varsha Varadhan ,&nbsp;Monica Shri Manikandan ,&nbsp;Kumaravel Kaliaperumal ,&nbsp;Thirunavukkarasu Palaniyandi ,&nbsp;Senthilkumar Kaliamoorthy ,&nbsp;Gomathy Baskar ,&nbsp;Safia Obaidur Rab ,&nbsp;Vishal M Balaramnavar ,&nbsp;Saravanan Kumarasamy","doi":"10.1016/j.prp.2025.155811","DOIUrl":"10.1016/j.prp.2025.155811","url":null,"abstract":"<div><div>Cancers are a class of disorders that entail uncontrollably unwanted cell development with dissemination. One in six fatalities globally is attributed to cancer, a global health issue. The analysis of the entire DNA sequence and how it expresses itself in tumor cells is known as cancer genomics. The development of novel cancer treatments has been facilitated because of the genomics method. COL10A1 gene, a short chain collagen, and an interstitial matrix component, acts as a predictive biomarker for cancer prognosis. Recognizing the fundamental consequences of mutations in the COL10A1 gene and its expression in cancer is crucial. Analyzing the COL10A1 gene expression with a data set and gene expression patterns shows the level of display of the tumor. Examining the therapeutic techniques of COL10A1 gene expression leads to early detection, screening, radiation therapy, and advanced developments. This review highlights the value of the COL10A1 gene in breast, gastric, pancreatic, lung, and colorectal cancers, emphasizing its role in gene expression patterns and therapeutic techniques.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155811"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952928","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":"STAT3-related lncRNAs in colorectal cancer progression; Special focus on immune cell’s evasion","authors":"Mohamed J. Saadh ,&nbsp;Junainah Abd Hamid ,&nbsp;Malathi H ,&nbsp;Syeda Wajida Kazmi ,&nbsp;Mareb Hamed Ahmed ,&nbsp;Ashish Sharma ,&nbsp;M.Ravi Kumar ,&nbsp;Beneen Husseen","doi":"10.1016/j.prp.2025.155810","DOIUrl":"10.1016/j.prp.2025.155810","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is globally ranked as the third leading cause of cancer-related deaths in both men and women. There is an urgent need for novel biomarkers to facilitate early diagnosis and enhance patient care, thereby improving treatment response and reducing mortality rates. Signal transducer and activator of transcription 3 (STAT3) is essential for controlling the anti-tumor immune response since it is a hub for several oncogenic signaling pathways. In the tumor environment, STAT3 is widely overactivated in both malignant and non-cancerous cells. It is involved in suppressing the expression of critical immune activation regulators and encouraging the synthesis of immunosuppressive substances. Long noncoding RNAs (lncRNAs), a kind of non-coding RNA, are critical for CRC development, apoptosis, and metastasis because they influence important signaling pathways such as STAT3 signaling and contribute to gene regulation at the epigenetic, transcriptional, and post-transcriptional levels. Moreover, lncRNAs have a significant role in modifying the TME and control the expression of important immunological checkpoints, such as PD-L1. Therefore, a comprehensive understanding of the regulatory roles of lncRNAs is crucial for identifying diagnostic, prognostic, and predictive biomarkers for CRC. Thus, the objective of the present review study is to provide a comprehensive overview of the interaction between the STAT3 signaling pathway and various lncRNAs, as well as their implications for apoptosis, metastasis, and immune evasion in CRC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155810"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971871","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":"Assessment of different U-Net backbones in segmenting colorectal adenocarcinoma from H&E histopathology","authors":"Sagarika Sengupta ,&nbsp;Genevieve Chyrmang ,&nbsp;Kangkana Bora ,&nbsp;Himanish Shekhar Das ,&nbsp;Aimin Li ,&nbsp;Bernardo Lemos ,&nbsp;Saurav Mallik","doi":"10.1016/j.prp.2025.155820","DOIUrl":"10.1016/j.prp.2025.155820","url":null,"abstract":"<div><div>Adenocarcinoma, the most prevalent type of colorectal cancer, makes up roughly 95 % of all cases and is associated with a notably high mortality rate. Owing to the various risk factors which might include personal choices and habits or genetic factors, the risk of developing the cancer for every individual might vary. However, given the statistics, the rate of acquiring the disease is pretty high. Therefore, based on the need for early detection and diagnosis of the disease, there is a pressing demand for an automated system to accurately identify adenocarcinoma in the colorectal region by utilizing the concept of binary segmentation wherein two classes are employed to indicate the presence as well as the absence of the condition. To address this, the project explored several deep learning-based segmentation methods—such as U-Net, Attention U-Net, U-Net with ResNet50 backbone, U-Net with MobileNet-v2 backbone, U-Net with EfficientNetB0 backbone, and U-Net with DenseNet121 backbone—to segment adenocarcinoma regions in histopathological images of the colon and rectum, which are essentially the various U-Net backbones. The performance of each method was then compared to identify the most effective approach, and subsequently, it was found that the U-Net with DenseNet121 backbone and U-Net with ResNet50 backbone performed better than the rest of the models in terms of accuracy with its respective training accuracy scores being 93.81 % and 93.39 % while the testing accuracy scores were 90.21 % and 89.81 %, respectively.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155820"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009678","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":"Clinicopathological analysis of anti-VEGF drug-associated renal thrombotic microangiopathy: A case series and review of the literature","authors":"Qianqian Han,&nbsp;Lin Li,&nbsp;Ziyao Li,&nbsp;Mei Yang,&nbsp;Song Lei,&nbsp;Yanyan Su,&nbsp;Huan Xu","doi":"10.1016/j.prp.2025.155824","DOIUrl":"10.1016/j.prp.2025.155824","url":null,"abstract":"<div><div>Anti-vascular endothelial growth factor-associated thrombotic microangiopathy (aVEGF-TMA) was recently discovered in patients with malignant tumors. Four aVEGF-TMA patients diagnosed by renal biopsy between 2018 and 2022 were identified, and all were females aged 30–62 years (mean age, 47 years). Two patients with malignant gastrointestinal stromal tumors who received sunitinib were analyzed. One patient was treated with bevacizumab plus regorafenib, which has never been reported before. Another patient had lung adenocarcinoma with multiple metastasis and was treated with bevacizumab. Proteinuria was often the first symptom, and the mean onset time was 23.25 months (7–36 months). Renal function was decreased in all patients, and nephrotic syndrome, hematuria, hypertension and anemia were present in some patients. Microscopically, both bevacizumab-TMAs and sunitinib-TMAs presented thrombi within dilated capillaries, mesangiolysis, double counters of the glomerular basement membrane and effaced or fused foot processes. Glomerulosclerosis and endothelial cell injury occurred in only some patients. Positive IgM deposits were observed in all aVEGF-TMAs, but IgA and C3 deposits were observed only in bevacizumab-TMAs. CD34 expression was absent around dilated capillaries containing thrombi, and immunostaining for fibrin/fibrinogen was positive; however, CD61 staining was negative in all patients. Thus, fibrin thrombi were suggested to be present in aVEGF-TMA. The mean follow-up time after renal biopsy was 19.5 months (range 14–32 months). One patient continued sunitinib treatment and eventually progressed to permanent dialysis, but tumor progression was controlled. The other three patients developed drug resistance, two patients discontinued aVEGF medication, and proteinuria decreased significantly. Notably, one patient recovered 14 months after withdrawal. The other patient who continued bevacizumab treatment had persistent proteinuria, and the tumor still progressed. In summary, renal function needs to be monitored in patients with malignant tumors who are receiving aVEGF drug treatment, especially females. Timely termination of related aVEGF administration after comprehensive assessment could alleviate their clinical symptoms.</div></div><div><h3>Data Availability</h3><div>Data are available from the corresponding Author upon reasonable request.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155824"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067244","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}