Pub Date : 2026-01-08DOI: 10.3760/cma.j.cn112151-20250727-00510
L He, Y Wang, P K Song, L Du, D Cui, D G Liu
<p><p><b>Objective:</b> To investigate the expression of cellular prion protein (PrPc) and tumor stem cell marker, CD44, in colorectal cancer, and to analyze their correlation with the metastasis and prognosis of colorectal cancer. <b>Methods:</b> A retrospective analysis was conducted on 212 colorectal cancer samples received by the Department of Pathology, Beijing Hospital, Beijing, China from August 2017 to February 2024. Immunohistochemical staining and immunofluorescence double staining were used to examine the expression of PrPc and CD44 in colorectal cancer. Their relationship with the clinical outcomes of colorectal cancer was analyzed. The expression of PrPc and CD44 was scored using the proportion of positive tumor cells and staining intensity, and the expression levels were divided into the 4 categories of negative, weakly positive, moderately positive, and strongly positive. The knockout of PrPc in colorectal cancer stem cells P6C was performed to assess cell growth and migration capacity, and to analyze the role of PrPc in tumor metastasis. <b>Results:</b> The study cohort comprised 212 patients, including 130 males and 82 females, with an age range of 33 to 96 years and a mean age of (64.7±12.7) years. According to the tumor-node-metastasis (TNM) staging system, the cases were distributed as follows: 26 cases in stage T1, 61 cases in T2, 58 cases in T3, and 67 cases in T4. Regarding lymph node status, 151 patients were free from lymph node metastasis, while 61 patients had lymph node metastasis. In terms of distant metastasis, 136 patients had no distant metastasis, and 76 patients were diagnosed with distant metastasis. Histopathological grading revealed 1 case of well-differentiated adenocarcinoma, 166 cases of moderately-differentiated adenocarcinoma, and 45 cases of poorly-differentiated adenocarcinoma. The percentage of PrPc-expressing cells in advanced tumors (T4, 88.1%, 59/67), poorly-differentiated tumors (82.2%, 37/45), tumors with lymph node metastasis (86.9%, 53/61) or distant metastasis (85.5%, 65/76) was higher than that in early-stage or well-differentiated tumors. The co-expression of PrPc and CD44 in advanced tumors (86.6%, 58/67), poorly-differentiated tumors (80.0%, 36/45), and tumors with lymph node metastasis (85.3%, 52/61) or distant metastasis (84.2%, 64/76) was also higher. Statistical analysis showed that the expression of PrPc alone and the co-expression of PrPc/CD44 were significantly correlated with tumor differentiation, T staging, lymph node metastasis, and distant metastasis (<i>P</i><0.05). Western blot analysis showed that PrPc knockout suppressed the expression of N-cadherin and Twist, metastasis-related proteins. Scratch assay and Transwell assay demonstrated that PrPc knockout inhibited the invasion and migration of cancer stem cells. Continuous cell counting revealed that PrPc knockout impaired the proliferation of colorectal cancer stem cells (<i>P</i><0.01). <b>Conclusions:</b> The expression of
{"title":"[Cellular prion protein expression and its correlation with pathological features in colorectal cancer].","authors":"L He, Y Wang, P K Song, L Du, D Cui, D G Liu","doi":"10.3760/cma.j.cn112151-20250727-00510","DOIUrl":"https://doi.org/10.3760/cma.j.cn112151-20250727-00510","url":null,"abstract":"<p><p><b>Objective:</b> To investigate the expression of cellular prion protein (PrPc) and tumor stem cell marker, CD44, in colorectal cancer, and to analyze their correlation with the metastasis and prognosis of colorectal cancer. <b>Methods:</b> A retrospective analysis was conducted on 212 colorectal cancer samples received by the Department of Pathology, Beijing Hospital, Beijing, China from August 2017 to February 2024. Immunohistochemical staining and immunofluorescence double staining were used to examine the expression of PrPc and CD44 in colorectal cancer. Their relationship with the clinical outcomes of colorectal cancer was analyzed. The expression of PrPc and CD44 was scored using the proportion of positive tumor cells and staining intensity, and the expression levels were divided into the 4 categories of negative, weakly positive, moderately positive, and strongly positive. The knockout of PrPc in colorectal cancer stem cells P6C was performed to assess cell growth and migration capacity, and to analyze the role of PrPc in tumor metastasis. <b>Results:</b> The study cohort comprised 212 patients, including 130 males and 82 females, with an age range of 33 to 96 years and a mean age of (64.7±12.7) years. According to the tumor-node-metastasis (TNM) staging system, the cases were distributed as follows: 26 cases in stage T1, 61 cases in T2, 58 cases in T3, and 67 cases in T4. Regarding lymph node status, 151 patients were free from lymph node metastasis, while 61 patients had lymph node metastasis. In terms of distant metastasis, 136 patients had no distant metastasis, and 76 patients were diagnosed with distant metastasis. Histopathological grading revealed 1 case of well-differentiated adenocarcinoma, 166 cases of moderately-differentiated adenocarcinoma, and 45 cases of poorly-differentiated adenocarcinoma. The percentage of PrPc-expressing cells in advanced tumors (T4, 88.1%, 59/67), poorly-differentiated tumors (82.2%, 37/45), tumors with lymph node metastasis (86.9%, 53/61) or distant metastasis (85.5%, 65/76) was higher than that in early-stage or well-differentiated tumors. The co-expression of PrPc and CD44 in advanced tumors (86.6%, 58/67), poorly-differentiated tumors (80.0%, 36/45), and tumors with lymph node metastasis (85.3%, 52/61) or distant metastasis (84.2%, 64/76) was also higher. Statistical analysis showed that the expression of PrPc alone and the co-expression of PrPc/CD44 were significantly correlated with tumor differentiation, T staging, lymph node metastasis, and distant metastasis (<i>P</i><0.05). Western blot analysis showed that PrPc knockout suppressed the expression of N-cadherin and Twist, metastasis-related proteins. Scratch assay and Transwell assay demonstrated that PrPc knockout inhibited the invasion and migration of cancer stem cells. Continuous cell counting revealed that PrPc knockout impaired the proliferation of colorectal cancer stem cells (<i>P</i><0.01). <b>Conclusions:</b> The expression of","PeriodicalId":35997,"journal":{"name":"中华病理学杂志","volume":"55 1","pages":"66-73"},"PeriodicalIF":0.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.3760/cma.j.cn112151-20250716-00476
Y Liu, L Lei, J Chen, W Li, A N Feng, F Q Meng
{"title":"[Fibroblast heterogeneity and functional roles in interstitial lung diseases: insights from histopathology and single-cell transcriptomics analyses].","authors":"Y Liu, L Lei, J Chen, W Li, A N Feng, F Q Meng","doi":"10.3760/cma.j.cn112151-20250716-00476","DOIUrl":"https://doi.org/10.3760/cma.j.cn112151-20250716-00476","url":null,"abstract":"","PeriodicalId":35997,"journal":{"name":"中华病理学杂志","volume":"54 12","pages":"1353-1359"},"PeriodicalIF":0.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.3760/cma.j.cn112151-20250626-00431
X Wei, J Y Chen, K Xin, Q Sun, F Q Meng, Z W Li
{"title":"[Esophageal gastrointestinal stromal tumor with MKRN1::BRAF gene fusion: report of a case].","authors":"X Wei, J Y Chen, K Xin, Q Sun, F Q Meng, Z W Li","doi":"10.3760/cma.j.cn112151-20250626-00431","DOIUrl":"10.3760/cma.j.cn112151-20250626-00431","url":null,"abstract":"","PeriodicalId":35997,"journal":{"name":"中华病理学杂志","volume":"54 12","pages":"1344-1346"},"PeriodicalIF":0.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.3760/cma.j.cn112151-20250326-00208
W J Ni, L Yang, L N Fan, Y Qin, J Zhang, R Wang
{"title":"[Splenorenal fusion in renal parenchyma: report of a case].","authors":"W J Ni, L Yang, L N Fan, Y Qin, J Zhang, R Wang","doi":"10.3760/cma.j.cn112151-20250326-00208","DOIUrl":"https://doi.org/10.3760/cma.j.cn112151-20250326-00208","url":null,"abstract":"","PeriodicalId":35997,"journal":{"name":"中华病理学杂志","volume":"54 12","pages":"1341-1343"},"PeriodicalIF":0.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.3760/cma.j.cn112151-20250403-00231
J Zhou, Y T Wang, L J Zhang, Y Cai, X Li, S D Yang
{"title":"[Clinicopathological and molecular genetic characteristics of multifocal micronodular pneumocyte hyperplasia (MMPH)].","authors":"J Zhou, Y T Wang, L J Zhang, Y Cai, X Li, S D Yang","doi":"10.3760/cma.j.cn112151-20250403-00231","DOIUrl":"10.3760/cma.j.cn112151-20250403-00231","url":null,"abstract":"","PeriodicalId":35997,"journal":{"name":"中华病理学杂志","volume":"54 12","pages":"1334-1337"},"PeriodicalIF":0.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.3760/cma.j.cn112151-20250722-00495
Y Q Liu
The experimental oncology accomplished a lot during last 70 years. The employment of earlier days'animal models for carcinogenesis, then the immunue deficient mice with human cell lines for invasion/metastasis and dormancy/recurrence were all benenfit from sharing of the collection of animal tumor strains and National Biomedical Cell-line Resource. The future data-driven and AI-assisted cancer research will also be firmly upholded by the resource center.
{"title":"[Experimental oncology:from collection of animal tumor strains to National Biomedical Cell-line Resource Center].","authors":"Y Q Liu","doi":"10.3760/cma.j.cn112151-20250722-00495","DOIUrl":"https://doi.org/10.3760/cma.j.cn112151-20250722-00495","url":null,"abstract":"<p><p>The experimental oncology accomplished a lot during last 70 years. The employment of earlier days'animal models for carcinogenesis, then the immunue deficient mice with human cell lines for invasion/metastasis and dormancy/recurrence were all benenfit from sharing of the collection of animal tumor strains and National Biomedical Cell-line Resource. The future data-driven and AI-assisted cancer research will also be firmly upholded by the resource center.</p>","PeriodicalId":35997,"journal":{"name":"中华病理学杂志","volume":"54 12","pages":"1253-1255"},"PeriodicalIF":0.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.3760/cma.j.cn112151-20250605-00388
S S Wang, M H Zheng, Y Wang, J J Zeng, L Wei, Z H Ma, F F Fu, Q Y Liu
<p><p><b>Objective:</b> To investigate the clinicopathological characteristics of lung transplantation and post-transplantation changes in patients with pneumoconiosis. <b>Methods:</b> A retrospective study was conducted to analyze the clinical and pathological data of 28 patients with pulmonary silicosis who underwent lung transplantation and were managed at the Department of Internal Medicine, Henan Provincial People's Hospital, Zhengzhou, China from January 2015 to December 2024. Among them, 8 patients underwent lung biopsy 6-20 months after transplantation to evaluate the histopathological changes of the recipient and the donor lungs post-transplantation. The expression of relevant indicators was examined using immunohistochemical EnVision staining, while presence of microorganisms was assessed using histochemical special staining. The patients were all followed up. <b>Results:</b> Among the 28 patients with pneumoconiosis who underwent lung transplantation, 26 were male and 2 were female, with a male-to-female ratio of 13∶1. Their ages ranged from 23 to 68 years, median 50.0 (46.0, 53.5) years. They were diagnosed with pneumoconiosis at local occupational disease prevention and control centers for 3 to 15 years (mean, 9.65 years), including 13 left single lung transplants and 15 right single lung transplants. Gross examination showed fleshy nodules with irregular cystic cavities at the periphery. The cut surfaces exhibited gray-brown color and firm texture. Microscopically, most alveolar structures of the lung were obliterated, with nodular or diffuse proliferation of collagen fibers accompanied by hyaline degeneration. Focal massive carbon dust deposition and massive silicotic fibrosis were observed, surrounded by lung parenchyma with emphysematous changes and localized bullae formation. Seven patients underwent re-biopsy after transplantation that showed extensive infiltration of inflammatory cells. In 4 cases, microscopy revealed complete coagulative necrosis, with negative acid-fast staining and TB-DNA results. Of the 4 cases, 3 cases exhibited Aspergillus infection confirmed by Grocott's methenamine silver and PAS stains, while 2 cases showed chronic bronchitis with squamous metaplasia. Follow-up revealed that 8 patients died of acute respiratory failure due to severe infection, while the remaining 20 demonstrated significant postoperative improvement in lung function. <b>Conclusions:</b> For patients with advanced pulmonary dust deposition disease who undergo lung transplantation, it is necessary to conduct standardized sampling and pathological assessment of the recipient lungs. In the early post-transplant period, the complications of re-biopsy tissues are mainly fungal infections. The combination of morphological manifestations and immunohistochemical detection is helpful to distinguish infection from rejection reactions. At the same time, it is essential to integrate clinical information and laboratory results to provide post-trans
{"title":"[Lung transplantation and post-transplantation changes in patients with pneumoconiosis: a clinicopathological analysis of 28 cases].","authors":"S S Wang, M H Zheng, Y Wang, J J Zeng, L Wei, Z H Ma, F F Fu, Q Y Liu","doi":"10.3760/cma.j.cn112151-20250605-00388","DOIUrl":"https://doi.org/10.3760/cma.j.cn112151-20250605-00388","url":null,"abstract":"<p><p><b>Objective:</b> To investigate the clinicopathological characteristics of lung transplantation and post-transplantation changes in patients with pneumoconiosis. <b>Methods:</b> A retrospective study was conducted to analyze the clinical and pathological data of 28 patients with pulmonary silicosis who underwent lung transplantation and were managed at the Department of Internal Medicine, Henan Provincial People's Hospital, Zhengzhou, China from January 2015 to December 2024. Among them, 8 patients underwent lung biopsy 6-20 months after transplantation to evaluate the histopathological changes of the recipient and the donor lungs post-transplantation. The expression of relevant indicators was examined using immunohistochemical EnVision staining, while presence of microorganisms was assessed using histochemical special staining. The patients were all followed up. <b>Results:</b> Among the 28 patients with pneumoconiosis who underwent lung transplantation, 26 were male and 2 were female, with a male-to-female ratio of 13∶1. Their ages ranged from 23 to 68 years, median 50.0 (46.0, 53.5) years. They were diagnosed with pneumoconiosis at local occupational disease prevention and control centers for 3 to 15 years (mean, 9.65 years), including 13 left single lung transplants and 15 right single lung transplants. Gross examination showed fleshy nodules with irregular cystic cavities at the periphery. The cut surfaces exhibited gray-brown color and firm texture. Microscopically, most alveolar structures of the lung were obliterated, with nodular or diffuse proliferation of collagen fibers accompanied by hyaline degeneration. Focal massive carbon dust deposition and massive silicotic fibrosis were observed, surrounded by lung parenchyma with emphysematous changes and localized bullae formation. Seven patients underwent re-biopsy after transplantation that showed extensive infiltration of inflammatory cells. In 4 cases, microscopy revealed complete coagulative necrosis, with negative acid-fast staining and TB-DNA results. Of the 4 cases, 3 cases exhibited Aspergillus infection confirmed by Grocott's methenamine silver and PAS stains, while 2 cases showed chronic bronchitis with squamous metaplasia. Follow-up revealed that 8 patients died of acute respiratory failure due to severe infection, while the remaining 20 demonstrated significant postoperative improvement in lung function. <b>Conclusions:</b> For patients with advanced pulmonary dust deposition disease who undergo lung transplantation, it is necessary to conduct standardized sampling and pathological assessment of the recipient lungs. In the early post-transplant period, the complications of re-biopsy tissues are mainly fungal infections. The combination of morphological manifestations and immunohistochemical detection is helpful to distinguish infection from rejection reactions. At the same time, it is essential to integrate clinical information and laboratory results to provide post-trans","PeriodicalId":35997,"journal":{"name":"中华病理学杂志","volume":"54 12","pages":"1304-1310"},"PeriodicalIF":0.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.3760/cma.j.cn112151-20251009-00666
Y P Liu, W T Yang
After the release of the guideline for HER2 testing in breast cancer (2024 version), in order to improve the implementation of the guidelines, the Chinese Breast Pathology Group conducted a nationwide survey, gathering feedback from pathologists across China. Based on this, we analyzed and summarized seven key issues commonly encountered in pathological practice. These issues include the heterogeneity of HER2 protein and gene expression, reporting of HER2-ultralow, testing and interpretation issues of HER2 low-level expression, the establishment of external controls for HER2 testing, the interpretation standards for rare staining patterns, and the role of new technologies in HER2-low expression testing. These findings reflect the effectiveness and challenges in the implementation of the guidelines and provide valuable insights for the further optimization of the HER2 testing guidelines in the future.
{"title":"[Hot issues after the release of the guideline for HER2 testing in breast cancer (2024 version)].","authors":"Y P Liu, W T Yang","doi":"10.3760/cma.j.cn112151-20251009-00666","DOIUrl":"https://doi.org/10.3760/cma.j.cn112151-20251009-00666","url":null,"abstract":"<p><p>After the release of the guideline for HER2 testing in breast cancer (2024 version), in order to improve the implementation of the guidelines, the Chinese Breast Pathology Group conducted a nationwide survey, gathering feedback from pathologists across China. Based on this, we analyzed and summarized seven key issues commonly encountered in pathological practice. These issues include the heterogeneity of HER2 protein and gene expression, reporting of HER2-ultralow, testing and interpretation issues of HER2 low-level expression, the establishment of external controls for HER2 testing, the interpretation standards for rare staining patterns, and the role of new technologies in HER2-low expression testing. These findings reflect the effectiveness and challenges in the implementation of the guidelines and provide valuable insights for the further optimization of the HER2 testing guidelines in the future.</p>","PeriodicalId":35997,"journal":{"name":"中华病理学杂志","volume":"54 12","pages":"1256-1261"},"PeriodicalIF":0.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.3760/cma.j.cn112151-20250319-00193
Y P Tian, Z X Ma, Y Zhuo, L N Xie, C H Wu, C Xu, J Cao, L S Ying, D Su
{"title":"[Analysis of clinicopathological and genetic characteristics of three cases of Li-Fraumeni syndrome].","authors":"Y P Tian, Z X Ma, Y Zhuo, L N Xie, C H Wu, C Xu, J Cao, L S Ying, D Su","doi":"10.3760/cma.j.cn112151-20250319-00193","DOIUrl":"10.3760/cma.j.cn112151-20250319-00193","url":null,"abstract":"","PeriodicalId":35997,"journal":{"name":"中华病理学杂志","volume":"54 12","pages":"1330-1333"},"PeriodicalIF":0.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.3760/cma.j.cn112151-20250328-00217
A J Hu, Y Liu, C R Liu
Objective: To investigate the clinical values of fluorescent PCR-capillary electrophoresis (PCR/CE) for detecting somatic mutations in the proofreading exonuclease domain of DNA polymerase epsilon (POLE-exo*) in endometrial carcinomas (EC), as compared with Sanger sequencing. Methods: A total of 280 EC cases diagnosed at the Department of Pathology at Peking University Third Hospital, Beijing, China from December 2022 to December 2023 were collected. Ten cases, which had previously been confirmed to harbor POLE pathogenic mutations through next-generation sequencing (NGS), were excluded. Subsequently, parallel sequencing using both PCR/CE and Sanger sequencing methods was conducted on the remaining 270 EC samples without prior POLE testing, aiming to examine 11 known pathogenic mutation-sites located within exons 9, 11, 13, and 14 of the POLE gene. NGS was then carried out on the EC cases in which the PCR/CE and/or Sanger sequencing results indicated the presence of POLE-exo*. Results: Among the 270 EC samples, POLE-exo* was detected in 4 cases (4/270, 1.5%) using Sanger sequencing. In contrast, the PCR/CE identified POLE-exo* in 12 cases (12/270, 4.4%). It was noteworthy that all cases in which POLE-exo* was detected through Sanger sequencing were also successfully identified using PCR/CE (4/4, with a detection rate of 100%). These results were further verified by NGS. The PCR/CE also uncovered an additional 8 cases (8/266, 3.0%) of POLE-exo* in the 266 samples that were negative for POLE mutations per Sanger sequencing. Of these 8 cases, 4 were validated using NGS, exhibiting variant allele frequency (VAF) below 10%, but tumor mutation burdens exceeding 10 mutations per megabase. However, due to small tumor sizes, NGS verification could not be performed on the remaining 4 PCR/CE-positive but Sanger-negative cases. Conclusion: The PCR/CE exhibits better sensitivity and detection capabilities than the Sanger sequencing in identifying POLE-exo* in EC samples, particularly in detecting low VAF.
{"title":"[Clinical value of fluorescent PCR-capillary electrophoresis for detecting POLE mutations in endometrial carcinoma].","authors":"A J Hu, Y Liu, C R Liu","doi":"10.3760/cma.j.cn112151-20250328-00217","DOIUrl":"https://doi.org/10.3760/cma.j.cn112151-20250328-00217","url":null,"abstract":"<p><p><b>Objective:</b> To investigate the clinical values of fluorescent PCR-capillary electrophoresis (PCR/CE) for detecting somatic mutations in the proofreading exonuclease domain of DNA polymerase epsilon (POLE-exo*) in endometrial carcinomas (EC), as compared with Sanger sequencing. <b>Methods:</b> A total of 280 EC cases diagnosed at the Department of Pathology at Peking University Third Hospital, Beijing, China from December 2022 to December 2023 were collected. Ten cases, which had previously been confirmed to harbor POLE pathogenic mutations through next-generation sequencing (NGS), were excluded. Subsequently, parallel sequencing using both PCR/CE and Sanger sequencing methods was conducted on the remaining 270 EC samples without prior POLE testing, aiming to examine 11 known pathogenic mutation-sites located within exons 9, 11, 13, and 14 of the POLE gene. NGS was then carried out on the EC cases in which the PCR/CE and/or Sanger sequencing results indicated the presence of POLE-exo*. <b>Results:</b> Among the 270 EC samples, POLE-exo* was detected in 4 cases (4/270, 1.5%) using Sanger sequencing. In contrast, the PCR/CE identified POLE-exo* in 12 cases (12/270, 4.4%). It was noteworthy that all cases in which POLE-exo* was detected through Sanger sequencing were also successfully identified using PCR/CE (4/4, with a detection rate of 100%). These results were further verified by NGS. The PCR/CE also uncovered an additional 8 cases (8/266, 3.0%) of POLE-exo* in the 266 samples that were negative for POLE mutations per Sanger sequencing. Of these 8 cases, 4 were validated using NGS, exhibiting variant allele frequency (VAF) below 10%, but tumor mutation burdens exceeding 10 mutations per megabase. However, due to small tumor sizes, NGS verification could not be performed on the remaining 4 PCR/CE-positive but Sanger-negative cases. <b>Conclusion:</b> The PCR/CE exhibits better sensitivity and detection capabilities than the Sanger sequencing in identifying POLE-exo* in EC samples, particularly in detecting low VAF.</p>","PeriodicalId":35997,"journal":{"name":"中华病理学杂志","volume":"54 12","pages":"1324-1329"},"PeriodicalIF":0.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}