{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T20:29:26Z","timestamp":1762374566128,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Flow cytometric analysis of cellular DNA content has prognostic importance in ovarian cancer and its measurement could contribute to clinical practice. The aim of this study was to compare serous cystadenoma and serous cystadenocarcinoma cases in terms of their flow cytometric analysis results. Methods: In total, 60 serous ovarian tumor cases (30 cases of ovarian serous cyst adenoma and 30 cases of ovarian serous cystadenocarcinoma) in paraffin blocks were extracted from hospital pathology archives for flow cytometric analysis. Cell cycle changes, aneuploidy ratio, and annexin V levels were compared. Results: The S phase cell ratio, proliferative index, aneuploidy cell ratio, and annexin V apoptotic index were significantly higher in the cancer group compared to the cystadenoma group. However, the G2\/M phase cell ratio was found to be similar in both groups. When the annexin V apoptotic index cutoff value was selected as 27.65%, the sensitivity was calculated as 90.0% and the specificity as 93.3% for predicting serous ovarian carcinoma (AUC, 0.872; p &lt; 0.001; 95% CI, 0.761\u20130.984). Conclusions: In serous cystadenocarcinoma cases, cell cycle activity was increased compared to serous cyst adenoma, but the similarity of G2\/M activities suggested that serous cystadenocarcinoma may be a member of the \u201cmetaneoplasia\u201d process. The detection of annexin V expression in ovarian tumors by flow cytometric analysis is a cheap, fast, and easy diagnostic method that can be used in the diagnosis of ovarian cancer. Annexin V expression is an effective biomarker with high sensitivity and specificity that could be used in the diagnosis of serous ovarian cancer.<\/jats:p>","DOI":"10.3390\/cancers17162691","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T10:59:01Z","timestamp":1755601141000},"page":"2691","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Comparison of the Flow Cytometric Analysis Results of Benign and Malignant Serous Tumors of the Ovary"],"prefix":"10.3390","volume":"17","author":[{"given":"Ozgur","family":"Ozdemir","sequence":"first","affiliation":[{"name":"Independent Researcher, Trabzon 61050, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustafa Emre","family":"Duygulu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon 61080, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yavuz","family":"Tekelioglu","sequence":"additional","affiliation":[{"name":"Department of Hystology and Embryology, Faculty of Medicine, Karadeniz Technical University, Trabzon 61080, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Safak","family":"Ersoz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Karadeniz Technical University, Trabzon 61080, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-4525","authenticated-orcid":false,"given":"Suleyman","family":"Guven","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Karadeniz Technical University, Trabzon 61080, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/ijgo.13878","article-title":"Cancer of the ovary, fallopian tube, and peritoneum: 2021 update","volume":"155","author":"Berek","year":"2021","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_2","first-page":"87","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","first-page":"284","article-title":"Ovarian cancer statistics, 2018","volume":"68","author":"Torre","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Koshiyama, M., Matsumura, N., and Konishi, I. (2014). Recent concepts of ovarian carcinogenesis: Type I and type II. Biomed. Res. Int., 2014.","DOI":"10.1155\/2014\/934261"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.humpath.2011.03.003","article-title":"Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer\u2014Shifting the paradigm","volume":"42","author":"Kurman","year":"2011","journal-title":"Hum. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.ajpath.2015.11.011","article-title":"The Dualistic Model of Ovarian Carcinogenesis: Revisited, Revised, and Expanded","volume":"186","author":"Kurman","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_7","first-page":"354","article-title":"Ovarian tumors in the reproductive age group","volume":"73","author":"Nowak","year":"2002","journal-title":"Ginekol. Pol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/j.1365-2184.2012.00845.x","article-title":"Programmed cell death pathways in cancer: A review of apoptosis, autophagy and programmed necrosis","volume":"45","author":"Ouyang","year":"2012","journal-title":"Cell Prolif."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nrm2312","article-title":"Apoptosis: Controlled demolition at the cellular level","volume":"9","author":"Taylor","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41580-018-0089-8","article-title":"Regulation of apoptosis in health and disease: The balancing act of BCL-2 family proteins","volume":"20","author":"Singh","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0022-1759(94)90373-5","article-title":"Rapid quantitation of apoptosis in pure and heterogeneous cell populations using flow cytometry","volume":"172","author":"Telford","year":"1994","journal-title":"J. Immunol. Methods"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S1534-5807(03)00090-X","article-title":"Annexin I is an endogenous ligand that mediates apoptotic cell engulfment","volume":"4","author":"Arur","year":"2003","journal-title":"Dev. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1097\/PGP.0000000000001018","article-title":"High-grade Serous Carcinoma Occurring in a Serous Cystadenoma on the Background of a Serous Tubal Intraepithelial Carcinoma (STIC)-like Lesion: A Case Report With Literature Review","volume":"43","author":"Novikov","year":"2024","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijgo.2013.10.001","article-title":"FIGO Committee on Gynecologic Oncology. Staging classification for cancer of the ovary, fallopian tube, and peritoneum","volume":"124","author":"Prat","year":"2014","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_15","first-page":"2428","article-title":"Simultaneous nuclear antigen and DNA content quantitation using paraffin-embedded colonic tissue and multiparameter flow cytometry","volume":"46","author":"Bauer","year":"1986","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/cyto.990100302","article-title":"Flow cytometry using paraffin-embedded tissue: Five years on","volume":"10","author":"Hedley","year":"1989","journal-title":"Cytometry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1177\/31.11.6619538","article-title":"Method for analysis of cellular DNA content of paraffin-embedded pathological material using flow cytometry","volume":"31","author":"Hedley","year":"1983","journal-title":"J. Histochem. Cytochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"359","DOI":"10.5114\/ceh.2023.132251","article-title":"Methotrexate-induced hepatotoxicity in rats and the therapeutic properties of vitamin E: A histopathologic and flowcytometric research","volume":"9","author":"Akman","year":"2023","journal-title":"Clin. Exp. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/1097-0320(20010215)46:1<28::AID-CYTO1034>3.0.CO;2-H","article-title":"Apoptotic index by Annexin V flow cytometry: Adjunct to morphologic and cytogenetic diagnosis of myelodysplastic syndromes","volume":"46","author":"Merchant","year":"2001","journal-title":"Cytometry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.4155\/bio-2021-0071","article-title":"A flow cytometric journey into cell cycle analysis","volume":"13","author":"Nair","year":"2021","journal-title":"Bioanalysis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1097\/00004347-199310000-00005","article-title":"Flow cytometry and AgNORs in benign, borderline, and malignant mucinous and serous tumours of the ovary","volume":"12","author":"Griffiths","year":"1993","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1002\/cncr.2820710429","article-title":"Flow cytometric evaluation of ovarian cancer","volume":"71","author":"Braly","year":"1993","journal-title":"Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.ijgo.2004.12.010","article-title":"Prognostic significance of DNA quantification by flow cytometry in ovarian tumors","volume":"88","author":"Kim","year":"2005","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1097\/00004347-198301000-00005","article-title":"Ploidy as a prognostic factor in ovarian cancer","volume":"2","author":"Friedlander","year":"1983","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1038\/sj.bjc.6601660","article-title":"A novel immunohistochemical method for estimating cell cycle phase distribution in ovarian serous neoplasms: Implications for the histopathological assessment of paraffin-embedded specimens","volume":"90","author":"Scott","year":"2004","journal-title":"Br. J. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gomes, F.C., Figueiredo, E.R.L., Araujo, E.N., Andrade, E.M., Carneiro, C.D.L., Almeida, G.M., Dias, H., Teixeira, L.I.B., Almeida, M.T., and Farias, M.F. (2023). Social, Genetics and Histopathological Factors Related to Titin (TTN) Gene Mutation and Survival in Women with Ovarian Serous Cystadenocarcinoma: Bioinformatics Analysis. Genes, 14.","DOI":"10.3390\/genes14051092"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Szafron, L.A., Iwanicka-Nowicka, R., Sobiczewski, P., Koblowska, M., Dansonka-Mieszkowska, A., Kupryjanczyk, J., and Szafron, L.M. (2024). The Diversity of Methylation Patterns in Serous Borderline Ovarian Tumors and Serous Ovarian Carcinomas. Cancers, 16.","DOI":"10.3390\/cancers16203524"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yamanaka, K., Koma, Y.I., Urakami, S., Takahashi, R., Nagamata, S., Omori, M., Torigoe, R., Yokoo, H., Nakanishi, T., and Ishihara, N. (2024). YKL40\/Integrin beta4 Axis Induced by the Interaction between Cancer Cells and Tumor-Associated Macrophages Is Involved in the Progression of High-Grade Serous Ovarian Carcinoma. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251910598"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9376","DOI":"10.3390\/cimb46090555","article-title":"Molecular Analysis of High-Grade Serous Ovarian Carcinoma Exhibiting Low-Grade Serous Carcinoma and Serous Borderline Tumor","volume":"46","author":"Kanno","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Balakrishnan, K., Chen, Y., and Dong, J. (2024). Amplification of Hippo Signaling Pathway Genes Is Governed and Implicated in the Serous Subtype-Specific Ovarian Carcino-Genesis. Cancers, 16.","DOI":"10.3390\/cancers16091781"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.4103\/0973-1482.187282","article-title":"Comparative expression of caspases and annexin V in benign and malignant ovarian tumors","volume":"14","author":"Hassan","year":"2018","journal-title":"J. Cancer Res. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9653194","DOI":"10.1155\/2017\/9653194","article-title":"EV-Associated MMP9 in High-Grade Serous Ovarian Cancer Is Preferentially Localized to Annexin V-Binding EVs","volume":"2017","author":"Reiner","year":"2017","journal-title":"Dis. Markers"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s10495-024-02074-w","article-title":"Mechanisms of apoptosis-related non-coding RNAs in ovarian cancer: A narrative review","volume":"30","author":"Wang","year":"2025","journal-title":"Apoptosis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.3892\/ijo.2017.3914","article-title":"Apoptosis is augmented in high-grade serous ovarian cancer by the combined inhibition of Bcl-2\/Bcl-xL and PARP","volume":"50","author":"Yokoyama","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"i4","DOI":"10.1093\/annonc\/mdw083","article-title":"Epithelial ovarian cancer: The molecular genetics of epithelial ovarian cancer","volume":"27","author":"Krzystyniak","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_36","first-page":"423","article-title":"Past, Present and Future of Flow Cytometry in Breast Cancer\u2014A Systematic Review","volume":"30","author":"Andreou","year":"2019","journal-title":"Electron. J. Int. Fed. Clin. Chem. Lab. Med. EJIFCC"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"106717","DOI":"10.1016\/j.ijsu.2022.106717","article-title":"Detection of cancer cells and tumor margins during colorectal cancer surgery by intraoperative flow cytometry","volume":"104","author":"Georvasili","year":"2022","journal-title":"Int. J. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Vartholomatos, E., Vartholomatos, G., Alexiou, G.A., and Markopoulos, G.S. (2021). The Past, Present and Future of Flow Cytometry in Central Nervous System Malignancies. Methods Protoc., 4.","DOI":"10.3390\/mps4010011"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"989S","DOI":"10.1177\/0145561320931989","article-title":"The Role of Intraoperative Flow Cytometry in Surgical Margins of Head and Neck Malignancies","volume":"100","author":"Vartholomatos","year":"2021","journal-title":"Ear Nose Throat J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Dorfman, D.M. (2025). The Flow Cytometric Evaluation of B- and T-Lymphoblastic Leukemia\/Lymphoma. Cancers, 17.","DOI":"10.3390\/cancers17071111"},{"key":"ref_41","unstructured":"(2025). NCCN Guidelines Version 2.2025. Acute Myeloid Leukemia (Age \u2265 18 Years), National Comprehensive Cancer Network."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/16\/2691\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:30:36Z","timestamp":1760034636000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/16\/2691"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,19]]},"references-count":41,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["cancers17162691"],"URL":"https:\/\/doi.org\/10.3390\/cancers17162691","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2025,8,19]]}}}