The 114th Annual Meeting of the United States and Canadian Academy of Pathology (USCAP) was held in Boston, Massachusetts, USA from March 22 to 27, 2025. The USCAP Annual Meeting is the world's largest and most influential academic conference for pathology professionals. Every year, thousands of professionals from hospitals, private laboratories, academic institutions and government agencies in pathology and related professional fields such as molecular, oncology and immunology attend the meeting. USCAP is one of the most influential international academic organizations in the field of pathology and a global leader in the dissemination of knowledge in the field of pathology, with more than 10,000 pathologist members. USCAP enriches, develops and disseminates knowledge about human pathology and comparative pathology by promoting research, organizing scientific conferences and publishing scientific journals. The research results from the Obstetrics and Gynecology Hospital Affiliated to Fudan University (Shanghai Red House Obstetrics and Gynecology Hospital), the team of Professor Yu Wenqiang from the Institute of Biomedical Sciences of Fudan University, and Professor Zhao Chengquan from the School of Medicine of the University of Pittsburgh - " PCDHGB7 "The Diagnostic Value of Gene Hypermethylation in Cervical Gastric Adenocarcinoma" was presented as a poster and academic exchange at the USCAP2025 Annual Meeting, which may rewrite the new pattern of diagnosis and treatment of cervical gastric adenocarcinoma .
Poster number: P172
Achievement Name
The Diagnoses Value of Hypermethylated PCDHGB7 in Endocervical Gastric-type Carcinoma
Brief Introduction
Cervical adenocarcinoma is one of the more common malignant tumors in the female reproductive system. Cervical gastric adenocarcinoma (GAS) is a special subtype that is highly invasive and unrelated to HPV . It is also the most common type of non-HPV-related cervical cancer. It is the second most common primary cervical adenocarcinoma after common cervical adenocarcinoma and a mucinous adenocarcinoma with gastric differentiation. Its morphological characteristics are very similar to benign lesions such as foliate endocervical glandular hyperplasia (LEGH), which makes clinical diagnosis very prone to misdiagnosis, seriously affecting the timing of treatment and rehabilitation effect of patients. Therefore, it is urgent to find a reliable diagnostic marker. The Obstetrics and Gynecology Hospital Affiliated to Fudan University and multiple institutions conducted a study to explore the differential diagnostic significance of hypermethylated PCDHGB7 for cervical gastric adenocarcinoma (GAS). From the perspective of clinical application, PCDHGB7 methylation detection is expected to become an important tool for diagnosing cervical adenocarcinoma, especially gastric adenocarcinoma. This detection technology can help doctors diagnose the condition more accurately and develop more targeted treatment plans for patients, thereby improving treatment outcomes and improving patient prognosis.
Background
Professor Yu Wenqiang's team at Fudan University discovered the pan-cancer marker UCOM based on GPS sequencing technology that covers more than 96% of the CpG sites in the human genome. Among them, PCDHGB7 , as a member of UCOM , is used to detect tumor-specific DNA methylation in cervical samples. Given that cervical gastric adenocarcinoma (GAS) is a highly invasive tumor that is not related to HPV, its well-differentiated cases may show mild morphological characteristics, which can be easily confused with other lesions and lead to misdiagnosis, especially it is difficult to distinguish from foliate endocervical glandular hyperplasia (LEGH) , and reliable markers are urgently needed for auxiliary diagnosis. Hypermethylation is of great significance in cervical squamous epithelial lesions, but there are few studies in glandular epithelial lesions. This study aims to evaluate whether hypermethylation of the PCDHGB7 gene can be used as a marker to distinguish GAS from similar lesions.
Study Design and Results
The research team selected 165 cervical lesion tissues, including 43 cases of common cervical adenocarcinoma (UEC), 41 cases of cervical gastric adenocarcinoma (GAS), 42 cases of phyllodes cervical glandular hyperplasia (LEGH) and 39 normal/benign tissues, and analyzed the methylation level of the PCDHGB7 gene. The study found that the methylation level of the PCDHGB7 gene in cervical adenocarcinoma was significantly higher than that in benign lesions, especially in gastric adenocarcinoma. By drawing the ROC curve for evaluation, PCDHGB7 methylation detection showed excellent performance in distinguishing cervical adenocarcinoma from benign lesions, with a sensitivity of 94.05% and a specificity of 96.30%. More importantly, the PCDHGB7 methylation detection method can effectively distinguish cervical gastric adenocarcinoma from phyllodes cervical glandular hyperplasia, providing a reliable molecular marker for clinical diagnosis and greatly improving the accuracy of diagnosis.
Conclusions
Hypermethylation of the PCDHGB7 gene can be used as a new marker to distinguish benign cervical lesions from adenocarcinoma (especially GAS), providing key support for accurate clinical diagnosis .
Research Interpretation
This study analyzed the hypermethylation level of the PCDHGB7 gene and found that it has high sensitivity and specificity in distinguishing benign lesions such as cervical gastric adenocarcinoma (GAS) and phyllodes cervical glandular hyperplasia (LEGH). The hypermethylation level of PCDHGB7 is significantly higher in cervical cancer (especially GAS) than in benign lesions, indicating that it may be used as an effective molecular marker for the diagnosis and differential diagnosis of cervical cancer.
This study provides new ideas for the early diagnosis of cervical cancer, especially for cervical gastric adenocarcinoma that is not related to HPV, which is usually difficult to accurately diagnose using traditional morphological methods. The detection of high methylation of PCDHGB7 may become an important tool in clinical diagnosis in the future , pushing the diagnostic threshold forward .
Professor Zhao Chengquan of the University of Pittsburgh School of Medicine ( first from left ), Professor Yu Wenqiang of Fudan University (second from left), Japanese pathologist Professor Yoshiki Mikami ( second from right ), and Dr. Zhong Fangfang of the Obstetrics and Gynecology Hospital of Fudan University ( first from right ) took a group photo in front of the poster
USCAP2025 live: Professor Yoshiki Mikami ( first from left ) , a Japanese gynecological pathologist who first defined cervical gastric adenocarcinoma, stopped in front of the poster for a long time , asked questions carefully and discussed the technical details with the poster author, and spoke highly of the research innovation.
Note: Professor Yoshiki Mikami of the Department of Diagnostic Pathology at Kumamoto University Hospital in Japan published a paper in 2007 titled “Gastric Morphology and Immunophenotype Predictors”. Poor Outcome in Mucinous Adenocarcinoma of The Uterine Cervix was published in 1975 , in which the pathological term "gastric-type adenocarcinoma of the cervix" was formally proposed, and it was believed that minimally differentiated adenocarcinoma (MDA) proposed by some scholars in 1975 was a highly differentiated form in its differentiation spectrum .
USCAP2025 live: Professor Yu Wenqiang of Fudan University (left) and Dr. Zhong Fangfang of Fudan University Affiliated Obstetrics and Gynecology Hospital ( right ) took a photo in front of the poster
Expert Profile
Professor Yu Wenqiang
Doctoral supervisor at Fudan University, chief scientist of the National "973" Project, distinguished professor of the " Changjiang Scholar " of the Ministry of Education, senior PI of the Epigenetics Center of the Institute of Biomedical Sciences of Fudan University, and chairman of the Methylation Tumor Marker Committee of the Chinese Anti-Cancer Association. He received his doctorate from the Fourth Military Medical University in 2001, worked as a postdoctoral fellow at Uppsala University in Sweden and Johns Hopkins University in the United States from 2001 to 2007, and became a faculty and associate research scientist at Columbia University in the United States in 2007. During his time abroad, he mainly engaged in the study of gene expression regulation and the relationship between non-coding RNA and DNA methylation. After returning to China, he focused on the role of whole genome DNA methylation detection in the occurrence of important clinical diseases and the activation function of nuclear miRNA. He developed GPS (guide positioning sequencing), a high-resolution whole-genome DNA methylation detection method with independent intellectual property rights, and analysis software, which has been granted domestic and international patents. GPS can achieve accurate methylation detection and high cytosine coverage (96%), solving the unresolved technical problems of WGBS methylation detection and proposing a new model of DNA methylation regulation of gene expression; he discovered a common marker for tumors, named Universal Cancer Only Marker (UCOM), which has been verified in more than 25 types of human tumors and applied to early diagnosis and recurrence monitoring of tumors, laying the foundation for the study of common mechanisms of tumors. He has been engaged in basic and clinical research in epigenetics for nearly 30 years , and has published more than 40 academic papers in journals such as Nature, Nature Genetics, and JAMA, and obtained 9 domestic and international patents .
Post time: Apr-15-2025