The expression of immunohistochemical biomarkers PAX8 and CD117 in platinum resistant ovarian cancer at Saiful Anwar General Hospital, Malang, Indonesia

Downloads
HIGHLIGHTS
- Ovarian cancer, a prevalent gynecologic malignancy affecting women, poses a significant challenge due to the development of resistance to platinum-based therapy in its management.
- PAX8 and CD117 have demonstrated potential as predictive biomarkers for platinum resistance in ovarian cancer; however, studies exploring their immunohistochemical expression in relation to platinum resistance in ovarian cancer patients remain limited.
- This study aims to evaluate the immunohistochemical expression of CD117 and PAX8 in ovarian cancer tissues and investigate their association with the emergence of platinum resistance.
ABSTRACT
Objective: Ovarian cancer, a prevalent gynecologic malignancy, frequently presents challenges due to platinum therapy resistance. This study aims to investigate a monitoring approach for post-operative ovarian carcinoma and evaluate the immunohistochemical expression of PAX8 and CD117 in ovarian cancer tissues, assessing their association with platinum resistance development.
Materials and Methods: Employing a cross-sectional observational analytical design, this study utilized consecutive sampling of patients meeting predefined inclusion and exclusion criteria. Tissue samples, obtained from biopsy or surgical procedures and processed into representative paraffin blocks, underwent immunohistochemical analysis at the Anatomical Pathology Department of Saiful Anwar Hospital, Malang, Indonesia. Expressions of PAX8 and CD117 were evaluated using immunohistochemistry. Diagnostic performance was assessed through receiver operating characteristic (ROC) curves and Youden index calculations to determine sensitivity and specificity.
Results: The study findings revealed that the area under the curve (AUC) for PAX8 and CD117 was 0.785 and 0.809, respectively. PAX8 expression exhibited a positive predictive value of 53.125%, negative predictive value of 87.50%, sensitivity of 18.75%, specificity of 51.85%, and accuracy of 60.0%. For CD117 expression, the corresponding values were 71.4%, 72.73%, 70%, 72.73%, and 70% for positive predictive value, negative predictive value, sensitivity, specificity, and accuracy, respectively.
Conclusion: The immunohistochemical expression of PAX8 and CD117 in ovarian cancer tissues may serve as prognostic biomarkers for platinum resistance. Despite these findings, the study acknowledges several limitations that warrant refinement in future research.
Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1. 0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11. Lyon, France: IARC; 2013. doi: 10.1002/ijc.29210.
Kumar V, Abbas AK, Fausto N, et al. Robbins and Cotran pathologic basis of disease. Professional edition e-book. Elsevier Health Sciences; 2014.
Ministry of Health, Republic of Indonesia. Data and Information Center. Profil kesehatan Indonesia 2012 [Indonesia health profile 2012]. Jakarta: Ministry of Health, Republic of Indonesia; 2013.
Yeldag G, Rice A, Del Río Hernández A. chemoresistance and the self-maintaining tumor microenvironment. Cancers (Basel). 2018;10(12): 471. doi: 10.3390/cancers10120471. PMID: 30487 436; PMCID: PMC6315745.
Wang J, Seebacher N, Shi H, et al. Novel strategies to prevent the development of multidrug resistance (MDR) in cancer. Oncotarget. 2017;8(48):84559-871. doi: 10.18632/oncotarget.19187. PMID: 2913 7448; PMCID: PMC5663620.
Sever M, Jones TD, Roth LM, et al. Expression of CD117 (c-kit) receptor in dysgerminoma of the ovary: diagnostic and therapeutic implications. Mod Pathol. 2005;18(11):1411-6. doi: 10.1038/ modpathol.3800463. PMID: 16056250.
Conic I, Stanojevic Z, Jankovic Velickovic L, et al. Epithelial ovarian cancer with CD117 phenotype is highly aggressive and resistant to chemotherapy. J Obstet Gynaecol Res. 2015;41(10):1630-7. doi: 10.1111/jog.12758. Epub 2015 Jul 14. PMID: 26177978.
Di Palma T, Zannini M. PAX8 as a potential target for ovarian cancer: what we know so far. Onco Targets Ther. 2022;15:1273-80. doi: 10.2147/OTT. S361511. PMID: 36275185; PMCID: PMC9584 354.
Adler EK, Corona RI, Lee JM, et al. The PAX8 cistrome in epithelial ovarian cancer. Oncotarget. 2017;8(65):108316-32. doi: 10.18632/oncotarget. 22718. PMID: 29312534; PMCID: PMC5752447.
Soriano AA, de Cristofaro T, Di Palma T, et al. PAX8 expression in high-grade serous ovarian cancer positively regulates attachment to ECM via Integrin β3. Cancer Cell Int. 2019;19:303. doi: 10.1186/s12935-019-1022-8. PMID: 31832016; PMCID: PMC6865034.
Chai HJ, Ren Q, Fan Q, Ye L, et al. PAX8 is a potential marker for the diagnosis of primary epithelial ovarian cancer. Oncol Lett. 2017;14(5): 5871-5. doi: 10.3892/ol.2017.6949. Epub 2017 Sep 15. PMID: 29113220; PMCID: PMC5661437.
Shnaider PV, Petrushanko IY, Aleshikova OI, et al. Expression level of CD117 (KIT) on ovarian cancer extracellular vesicles correlates with tumor aggressiveness. Front Cell Dev Biol. 2023;11:105 7484. doi: 10.3389/fcell.2023.1057484. PMID: 36875773; PMCID: PMC9978408.
Yang B, Yan X, Liu L, et al. Overexpression of the cancer stem cell marker CD117 predicts poor prognosis in epithelial ovarian cancer patients: evidence from meta-analysis. Onco Targets Ther. 2017;10:2951-61. doi: 10.2147/OTT.S136549. PMID: 28652777; PMCID: PMC5476715.
Lukanovic D, Kobal B, Cerne K. Ovarian cancer: treatment and resistance to pharmacotherapy. Reprod Med. 2022;3(2):127-40. doi: 10.3390/ reprodmed3020011.
Havasi A, Cainap SS, Havasi AT, et al. Ovarian cancer-insights into platinum resistance and overcoming it. Medicina (Kaunas). 2023;59(3):544. doi: 10.3390/medicina59030544. PMID: 36984544; PMCID: PMC10057458.
Khan MA, Vikramdeo KS, Sudan SK, et al. Platinum-resistant ovarian cancer: From drug resistance mechanisms to liquid biopsy-based biomarkers for disease management. Semin Cancer Biol. 2021;77:99-109. doi: 10.1016/j.semcancer. 2021.08.005. Epub 2021 Aug 18. PMID: 34418 576; PMCID: PMC8665066.
Li J, Zou G, Wang W, et al. Treatment options for recurrent platinum-resistant ovarian cancer: A systematic review and Bayesian network meta-analysis based on RCTs. Front Oncol. 2023;13: 1114484. doi: 10.3389/fonc.2023.1114484. PMID: 37114128; PMCID: PMC10126232.
Atallah GA, Kampan NC, Chew KT, et al. Predicting prognosis and platinum resistance in ovarian cancer: Role of immunohistochemistry biomarkers. Int J Mol Sci. 2023;24(3):1973. doi: 10.3390/ijms24031973. PMID: 36768291; PMCID: PMC9916805.
Damia G, Broggini M. Platinum resistance in ovarian cancer: Role of DNA repair. Cancers (Basel). 2019;11(1):119. doi: 10.3390/cancers1101 0119. PMID: 30669514; PMCID: PMC6357127.
Awada A, Ahmad S, McKenzie ND, et al. Immunotherapy in the treatment of platinum-resistant ovarian cancer: Current perspectives. Onco Targets Ther. 2022;15:853-66. doi: 10.2147/ OTT.S335936. PMID: 35982728; PMCID: PMC9379118.

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
1. Copyright of the article is transferred to the journal, by the knowledge of the author, whilst the moral right of the publication belongs to the author.
2. The legal formal aspect of journal publication accessibility refers to Creative Commons Attribution-Non Commercial-Share alike (CC BY-NC-SA), (https://creativecommons.org/licenses/by-nc-sa/4.0/)
3. The articles published in the journal are open access and can be used for non-commercial purposes. Other than the aims mentioned above, the editorial board is not responsible for copyright violation
The manuscript authentic and copyright statement submission can be downloaded ON THIS FORM.