Elif Ozsagir, Mustafa E Ercin, Figen Celep Eyuboglu, Mehmet A Osmanagaoglu
{"title":"P53 Puzzle: WWP1 and PARC Immunohistochemistry Illuminate New Pathways for Serous Ovarian Cancer.","authors":"Elif Ozsagir, Mustafa E Ercin, Figen Celep Eyuboglu, Mehmet A Osmanagaoglu","doi":"10.1097/PAI.0000000000001260","DOIUrl":null,"url":null,"abstract":"<p><p>High-grade serous carcinoma is categorized based on p53 mutation status. A relationship is known to exist between p53 mutations and p53 immunoexpression patterns, including overexpression, complete absence, cytoplasmic, and wild-type patterns. The ubiquitin ligases WWP1 and PARC, known to regulate p53 activation, are hypothesized to influence the pathogenesis of serous ovarian tumors. This retrospective study examined 7 low-grade serous carcinomas, 38 high-grade serous carcinomas, and 15 serous cystadenomas, with immunohistochemical analyses performed for WWP1, PARC, and p53. High-grade serous carcinoma cases were classified into wild-type, cytoplasmic, complete absence, or overexpression categories based on p53 immunohistochemistry. PARC and WWP1 expressions were compared across p53 categories and diagnoses. Results showed a statistically significant reduction in WWP1 and PARC expression in serous carcinomas, with the most pronounced loss observed in high-grade cases. Among morphologically classified high-grade carcinomas, 17 overexpression, 11 complete absence, 6 wild-type, and 4 cytoplasmic p53 cases were identified. A statistically significant relationship was found between PARC, WWP1, and p53 status. Higher expression levels of PARC and WWP1 were detected in p53 wild-type cases, whereas lower expression levels were associated with cases exhibiting p53 overexpression and complete absence. This study suggests that PARC and WWP1 play a role in the pathogenesis of high-grade serous ovarian carcinoma, potentially mediated by p53, making them promising targets for treatment and prognostic markers in serous ovarian cancer.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.3000,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Applied Immunohistochemistry & Molecular Morphology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/PAI.0000000000001260","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
High-grade serous carcinoma is categorized based on p53 mutation status. A relationship is known to exist between p53 mutations and p53 immunoexpression patterns, including overexpression, complete absence, cytoplasmic, and wild-type patterns. The ubiquitin ligases WWP1 and PARC, known to regulate p53 activation, are hypothesized to influence the pathogenesis of serous ovarian tumors. This retrospective study examined 7 low-grade serous carcinomas, 38 high-grade serous carcinomas, and 15 serous cystadenomas, with immunohistochemical analyses performed for WWP1, PARC, and p53. High-grade serous carcinoma cases were classified into wild-type, cytoplasmic, complete absence, or overexpression categories based on p53 immunohistochemistry. PARC and WWP1 expressions were compared across p53 categories and diagnoses. Results showed a statistically significant reduction in WWP1 and PARC expression in serous carcinomas, with the most pronounced loss observed in high-grade cases. Among morphologically classified high-grade carcinomas, 17 overexpression, 11 complete absence, 6 wild-type, and 4 cytoplasmic p53 cases were identified. A statistically significant relationship was found between PARC, WWP1, and p53 status. Higher expression levels of PARC and WWP1 were detected in p53 wild-type cases, whereas lower expression levels were associated with cases exhibiting p53 overexpression and complete absence. This study suggests that PARC and WWP1 play a role in the pathogenesis of high-grade serous ovarian carcinoma, potentially mediated by p53, making them promising targets for treatment and prognostic markers in serous ovarian cancer.
期刊介绍:
Applied Immunohistochemistry & Molecular Morphology covers newly developed identification and detection technologies, and their applications in research and diagnosis for the applied immunohistochemist & molecular Morphologist.
Official Journal of the International Society for Immunohistochemisty and Molecular Morphology.