CCNE1 EXPRESSION AND CA-125 LEVELS IN HIGH GRADE SEROUS CARCINOMA OVARY AT MOHAMMAD HOESIN HOSPITAL PALEMBANG ; A SINGLE-INSTITUTION DESCRIPTIVE STUDY
Main Article Content
High grade serous carcinoma (HGSC) of the ovary is the dominant subtype causing death from ovarian cancer. CCNE1 amplification occurs in 20% of ovarian HGSC and is associated with recurrence after platinum chemotherapy. Assessment of CCNE1 expression can be a screening for CCNE1 amplification. Measurement of CA-125 levels is routinely used for treatment monitoring and recurrence of HGSC patients. This study aims to assess CCNE1 expression, demographic characteristics and CA-125 levels of ovarian HGSC patients. Of the 31 HGSC patients, the study subjects were dominated by patients aged >50 years (61.3%), clinical stage FIGO III (64.5%), CCNE1 overexpression (71%), preoperative CA-125 levels ≥500 U/ml (77.4%) and postchemotherapy CA-125 levels <35 U/ml (58.1%).
Keywords:
HGSC
CCNE1 expression
CA-125
1. Aziz D, Etemadmoghadam D, Caldon CE, Au-Yeung G , Deng N, Hutchinson R , et al. 19q12 amplified and non-amplified subsets of high grade serous ovarian cancer with overexpression of cyclin E1 differ in their molecular drivers and clinical outcomes. Gynecol Oncol 2018;151(2):327-36.
2. Azzalini E, Stanta G, Canzonieri V, Bonin S. Overview of tumor heterogeneity in high-grade serous ovarian cancers. Int J Mol Sci 2023; 24(20):1-14.
3. Bachmann R, Brucker S, Stäbler A, et al. Prognostic relevance of high pretreatment ca125 levels in primary serous ovarian cancer. Mol Clin Oncol 2020;14(1):1-10.
4. Barmon D, Patra S, Nandwani M, Jethani R, Kataki AC. Critical Analysis of Advanced High-Grade Serous Epithelial Ovarian Cancer in Women: An Experience of 100 Cases from a Regional Cancer Center in Northeast India. South Asian J Cancer 2023;12(4):334-40.
5. Berek JS, Renz M, Kehoe S, Kumar L, Friedlander M. Cancer of the ovary, fallopian tube, and peritoneum: 2021 update. Int J Gynecol Obstet 2021;155(51):61-85.
6. Caldon CE, Musgrove EA. Distinct and redundant functions of cyclin E1 and cyclin E2 in development and cancer. Cell Div 2010;5(9):1-13.
7. Ch S, V. P. G, G. A. Role of CA 125 in predicting pathological response and recurrence in advanced stage non mucinous epithelial ovarian cancer. Int J Reprod Contraception, Obstet Gynecol 2022;11(11):1-6.
8. Chan AMY, Enwere E, McIntyre JB, Wilson H, Nwaroh C, Wiebe N, et al. Combined CCNE1 high-level amplification and overexpression is associated with unfavourable outcome in tubo-ovarian high-grade serous carcinoma. J Pathol Clin Res 2020;6(4):252-62.
9. Chan JK, Tian C, Kesterson JP, Lin KY, Darcy K, Richardson MT, et al. Gynecologic Oncology Preoperative and pre-chemotherapy CA-125 levels in high-risk early-stage ovarian cancer – An NRG / GOG study. Gynecol Oncol 2024;181:54-9.
10. Charkhchi P, Cybulski C, Gronwald J, Wong FO, Narod SA, Akbari MA. CA125 and Ovarian Cancer: A Comprehensive Review. Cancers (Basel) 2020;12(12):3730
11. Chen M, Jin Y, Bi Y, Yin J, Wang Y, Pan L. A survival analysis comparing women with ovarian low-grade serous carcinoma to those with high-grade histology. Onco Targets Ther 2014;7:1891-9.
12. Da Costa AABA, Do Canto LM, Larsen SJ, Ribeiro ARG, Stecca CE, Petersen AH, et al. Genomic profiling in ovarian cancer retreated with platinum based chemotherapy presented homologous recombination deficiency and copy number imbalances of CCNE1 and RB1 genes. BMC Cancer 2019;19(1):1-10.
13. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Pineros M, Znaor A, et al. Cancer statistics for the year 2020: An overview. Int J Cancer 2021;149(4):778-89.
14. Fraser CC, Jia B, Hu G, Johani LIA, Fritz-Klaus R, Ham JD, et al. Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125. J Immunol 2022;208(9):2227-38.
15. Hirst J, Crow J, Godwin A. Ovarian Cancer Genetics: Subtypes and Risk Factors. Ovarian Cancer - From Pathog to Treat. Published online 2018:3-38. doi:10.5772/intechopen.72705
16. Hsu CF, Seenan V, Wang LY, Chen PC, Ding DC, Chu TY. Human peritoneal fluid exerts ovulation- and nonovulation-sourced oncogenic activities on transforming fallopian tube epithelial cells. Cancer Cell Int 2024;24(1):1-12.
17. Kang EY, Weir A, Meagher NS, Farrington K, Nelson GS, Ghatage P, et al. CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An ovarian tumor tissue analysis consortium study. Cancer 2023;129(5):697-713.
18. Kanska J, Zakhour M, Taylor-Harding B, Karlan BY, Wiedemeyer WR. Cyclin E as a potential therapeutic target in high grade serous ovarian cancer. Gynecol Oncol 2016;143(1):152
19. Karst AM, Jones PM, Vena N, Ligon AH, Liu JF, Hirsch MS, et al. Cyclin E1 deregulation occurs early in secretory cell transformation to promote formation of fallopian tube-derived high-grade serous ovarian cancers. Cancer Res 2014;74(4):1141-52.
20. Kok YP, Guerrero Llobet S, Schoonen PM, Everts M, Bhattacharya A, Fehrmann RSN, et al. Overexpression of Cyclin E1 or Cdc25A leads to replication stress, mitotic aberrancies, and increased sensitivity to replication checkpoint inhibitors. Oncogenesis 2020;9(10):1-15.
21. Lee J, Kim JM, Lee YH, Chong GO, Hong DG. Correlation between Clinical Outcomes and Serum CA-125 Levels after Standard Treatment for Epithelial Ovarian Cancer. Anticancer Res 2022;42(1):349-53
22. Lee M, Chang MY, Yoo H, Lee KY, Chay DB, Cho H, et al. Clinical significance of CA125 level after the first cycle of chemotherapy on survival of patients with advanced ovarian cancer. Yonsei Med J 2016;57(3):580-87.
23. Lisio MA, Fu L, Goyeneche A, Gao ZH, Telleria C. High-grade serous ovarian cancer: Basic sciences, clinical and therapeutic standpoints. Int J Mol Sci 2019;20(9):1-33.
24. M Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: Epidemiology and risk factors. Int J Womens Health 2019;11(7):287-99.
25. Mai J, Yang L, Xie HJ, Li YY, Wang X, Liu XX. Molecular mechanisms of platinum‑based chemotherapy resistance in ovarian cancer (Review). Oncol Rep 2022;47(4):1-11.
26. Margolis B, Dao F, Licciardi M, Misirlioglu S, Olvera N, Ramaswami S, et al. CCNE1 amplification among metastatic sites in patients with gynecologic high-grade serous carcinoma. Gynecol Oncol Reports 2021;37:1-5.
27. Martin-Hirsch PL, Martin-Hirsch PL, Martin FL. The evolving role of MUC16 (CA125) in the transformation of ovarian cells and the progression of neoplasia. Carcinogenesis 2021;42(3):327-43.
28. Mcmullen M, Madariaga A, Lheureux S. New approaches for targeting platinum-resistant ovarian cancer. Semin Cancer Biol 2021;77(12):167-81.
29. Morales-Vásquez F, Pedernera E, Reynaga-Obregón J, Lopez-Basave HN, Gomora MJ, Carlon E, et al. High levels of pretreatment CA125 are associated to improved survival in high grade serous ovarian carcinoma. J Ovarian Res 2016;9(1):1-6.
30. Muhammad SA, Olaoye SO, Umar FK. Are preoperative serum cancer antigen 125 levels a prognostic factor for outcome in epithelial ovarian cancer ? A systematic review. Niger Med J 2024;65(2):108-18.
31. Nakayama N, Nakayama K, Shamima Y, Ishikawa M, Katagiri A, Iida K et al. Gene amplification CCNE1 is related to poor survival and potential therapeutic target in ovarian cancer. Cancer. 2010;116(11):2621-34.
32. Rema P, John ER, Samabasivan S, Prahladan A, George P, Ranjith JS, et al. Evaluation of Computed Tomography Scan and CA 125 Response in Predicting Operability in Advanced Ovarian Cancer and Assessing Survival Outcome in Interval Cytoreductive Surgery. Indian J Surg Oncol 2019;10(3):426-34.
33. Ribeiro ARG, Salvadori MM, De Brot L,Bovolin G, Mantoan H, Ilelis F, et al. Retrospective analysis of the role of cyclin E1 overexpression as a predictive marker for the efficacy of bevacizumab in platinum-sensitive recurrent ovarian cancer. Ecancermedicalscience 2021;15:1-17.
34. Stronach EA, Paul J, Timms KM, Hughes E, Brown K, Neff C, et al. Biomarker assessment of HR deficiency, tumor BRCA1/2 mutations, and CCNE1 copy number in ovarian cancer: Associations with clinical outcome following platinum monotherapy. Mol Cancer Res 2018;16(7):1103-11.
35. Talbot T, Lu H, Aboagye EO. Amplified therapeutic targets in high-grade serous ovarian carcinoma – a review of the literature with quantitative appraisal. Cancer Gene Ther 2023;30(7):955-63.
36. Tangdiung Y, Masadah R, Julian B, Wahid S, Vita G. Clinicopathological Characteristics of high and low-grade Ovarian Serous Carcinoma. IJSBAR 2022;62(1):275-80.
37. Tu M, Gao X, Guo T, Lu W, Xu J. Clinicopathological and prognostic factor analyses of primary fallopian tube carcinoma and high-grade serous ovarian cancer. World J Surg Oncol 2025;23(1):1-10.
38. Wu NYY, Fang C, Huang HS, Wang J, Chu TY. Natural history of ovarian high-grade serous carcinoma from time effects of ovulation inhibition and progesterone clearance of p53-defective lesions. Mod Pathol 2020;33(1):29-37.
39. Zhang M, Cheng S, Jin Y, Zhao Y, Wang Y. Roles of CA125 in diagnosis, prediction, and oncogenesis of ovarian cancer. Biochim Biophys Acta - Rev Cancer 2021;1875(2):1-11.
40. Zhao H, Wang J, Zhang Y, Yuan M, Yang S, Lisong L, et al. Prognostic values of CCNE1 amplification and overexpression in cancer patients: A systematic review and meta-analysis. J Cancer 2018;9(13):2397-407.
2. Azzalini E, Stanta G, Canzonieri V, Bonin S. Overview of tumor heterogeneity in high-grade serous ovarian cancers. Int J Mol Sci 2023; 24(20):1-14.
3. Bachmann R, Brucker S, Stäbler A, et al. Prognostic relevance of high pretreatment ca125 levels in primary serous ovarian cancer. Mol Clin Oncol 2020;14(1):1-10.
4. Barmon D, Patra S, Nandwani M, Jethani R, Kataki AC. Critical Analysis of Advanced High-Grade Serous Epithelial Ovarian Cancer in Women: An Experience of 100 Cases from a Regional Cancer Center in Northeast India. South Asian J Cancer 2023;12(4):334-40.
5. Berek JS, Renz M, Kehoe S, Kumar L, Friedlander M. Cancer of the ovary, fallopian tube, and peritoneum: 2021 update. Int J Gynecol Obstet 2021;155(51):61-85.
6. Caldon CE, Musgrove EA. Distinct and redundant functions of cyclin E1 and cyclin E2 in development and cancer. Cell Div 2010;5(9):1-13.
7. Ch S, V. P. G, G. A. Role of CA 125 in predicting pathological response and recurrence in advanced stage non mucinous epithelial ovarian cancer. Int J Reprod Contraception, Obstet Gynecol 2022;11(11):1-6.
8. Chan AMY, Enwere E, McIntyre JB, Wilson H, Nwaroh C, Wiebe N, et al. Combined CCNE1 high-level amplification and overexpression is associated with unfavourable outcome in tubo-ovarian high-grade serous carcinoma. J Pathol Clin Res 2020;6(4):252-62.
9. Chan JK, Tian C, Kesterson JP, Lin KY, Darcy K, Richardson MT, et al. Gynecologic Oncology Preoperative and pre-chemotherapy CA-125 levels in high-risk early-stage ovarian cancer – An NRG / GOG study. Gynecol Oncol 2024;181:54-9.
10. Charkhchi P, Cybulski C, Gronwald J, Wong FO, Narod SA, Akbari MA. CA125 and Ovarian Cancer: A Comprehensive Review. Cancers (Basel) 2020;12(12):3730
11. Chen M, Jin Y, Bi Y, Yin J, Wang Y, Pan L. A survival analysis comparing women with ovarian low-grade serous carcinoma to those with high-grade histology. Onco Targets Ther 2014;7:1891-9.
12. Da Costa AABA, Do Canto LM, Larsen SJ, Ribeiro ARG, Stecca CE, Petersen AH, et al. Genomic profiling in ovarian cancer retreated with platinum based chemotherapy presented homologous recombination deficiency and copy number imbalances of CCNE1 and RB1 genes. BMC Cancer 2019;19(1):1-10.
13. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Pineros M, Znaor A, et al. Cancer statistics for the year 2020: An overview. Int J Cancer 2021;149(4):778-89.
14. Fraser CC, Jia B, Hu G, Johani LIA, Fritz-Klaus R, Ham JD, et al. Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125. J Immunol 2022;208(9):2227-38.
15. Hirst J, Crow J, Godwin A. Ovarian Cancer Genetics: Subtypes and Risk Factors. Ovarian Cancer - From Pathog to Treat. Published online 2018:3-38. doi:10.5772/intechopen.72705
16. Hsu CF, Seenan V, Wang LY, Chen PC, Ding DC, Chu TY. Human peritoneal fluid exerts ovulation- and nonovulation-sourced oncogenic activities on transforming fallopian tube epithelial cells. Cancer Cell Int 2024;24(1):1-12.
17. Kang EY, Weir A, Meagher NS, Farrington K, Nelson GS, Ghatage P, et al. CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An ovarian tumor tissue analysis consortium study. Cancer 2023;129(5):697-713.
18. Kanska J, Zakhour M, Taylor-Harding B, Karlan BY, Wiedemeyer WR. Cyclin E as a potential therapeutic target in high grade serous ovarian cancer. Gynecol Oncol 2016;143(1):152
19. Karst AM, Jones PM, Vena N, Ligon AH, Liu JF, Hirsch MS, et al. Cyclin E1 deregulation occurs early in secretory cell transformation to promote formation of fallopian tube-derived high-grade serous ovarian cancers. Cancer Res 2014;74(4):1141-52.
20. Kok YP, Guerrero Llobet S, Schoonen PM, Everts M, Bhattacharya A, Fehrmann RSN, et al. Overexpression of Cyclin E1 or Cdc25A leads to replication stress, mitotic aberrancies, and increased sensitivity to replication checkpoint inhibitors. Oncogenesis 2020;9(10):1-15.
21. Lee J, Kim JM, Lee YH, Chong GO, Hong DG. Correlation between Clinical Outcomes and Serum CA-125 Levels after Standard Treatment for Epithelial Ovarian Cancer. Anticancer Res 2022;42(1):349-53
22. Lee M, Chang MY, Yoo H, Lee KY, Chay DB, Cho H, et al. Clinical significance of CA125 level after the first cycle of chemotherapy on survival of patients with advanced ovarian cancer. Yonsei Med J 2016;57(3):580-87.
23. Lisio MA, Fu L, Goyeneche A, Gao ZH, Telleria C. High-grade serous ovarian cancer: Basic sciences, clinical and therapeutic standpoints. Int J Mol Sci 2019;20(9):1-33.
24. M Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: Epidemiology and risk factors. Int J Womens Health 2019;11(7):287-99.
25. Mai J, Yang L, Xie HJ, Li YY, Wang X, Liu XX. Molecular mechanisms of platinum‑based chemotherapy resistance in ovarian cancer (Review). Oncol Rep 2022;47(4):1-11.
26. Margolis B, Dao F, Licciardi M, Misirlioglu S, Olvera N, Ramaswami S, et al. CCNE1 amplification among metastatic sites in patients with gynecologic high-grade serous carcinoma. Gynecol Oncol Reports 2021;37:1-5.
27. Martin-Hirsch PL, Martin-Hirsch PL, Martin FL. The evolving role of MUC16 (CA125) in the transformation of ovarian cells and the progression of neoplasia. Carcinogenesis 2021;42(3):327-43.
28. Mcmullen M, Madariaga A, Lheureux S. New approaches for targeting platinum-resistant ovarian cancer. Semin Cancer Biol 2021;77(12):167-81.
29. Morales-Vásquez F, Pedernera E, Reynaga-Obregón J, Lopez-Basave HN, Gomora MJ, Carlon E, et al. High levels of pretreatment CA125 are associated to improved survival in high grade serous ovarian carcinoma. J Ovarian Res 2016;9(1):1-6.
30. Muhammad SA, Olaoye SO, Umar FK. Are preoperative serum cancer antigen 125 levels a prognostic factor for outcome in epithelial ovarian cancer ? A systematic review. Niger Med J 2024;65(2):108-18.
31. Nakayama N, Nakayama K, Shamima Y, Ishikawa M, Katagiri A, Iida K et al. Gene amplification CCNE1 is related to poor survival and potential therapeutic target in ovarian cancer. Cancer. 2010;116(11):2621-34.
32. Rema P, John ER, Samabasivan S, Prahladan A, George P, Ranjith JS, et al. Evaluation of Computed Tomography Scan and CA 125 Response in Predicting Operability in Advanced Ovarian Cancer and Assessing Survival Outcome in Interval Cytoreductive Surgery. Indian J Surg Oncol 2019;10(3):426-34.
33. Ribeiro ARG, Salvadori MM, De Brot L,Bovolin G, Mantoan H, Ilelis F, et al. Retrospective analysis of the role of cyclin E1 overexpression as a predictive marker for the efficacy of bevacizumab in platinum-sensitive recurrent ovarian cancer. Ecancermedicalscience 2021;15:1-17.
34. Stronach EA, Paul J, Timms KM, Hughes E, Brown K, Neff C, et al. Biomarker assessment of HR deficiency, tumor BRCA1/2 mutations, and CCNE1 copy number in ovarian cancer: Associations with clinical outcome following platinum monotherapy. Mol Cancer Res 2018;16(7):1103-11.
35. Talbot T, Lu H, Aboagye EO. Amplified therapeutic targets in high-grade serous ovarian carcinoma – a review of the literature with quantitative appraisal. Cancer Gene Ther 2023;30(7):955-63.
36. Tangdiung Y, Masadah R, Julian B, Wahid S, Vita G. Clinicopathological Characteristics of high and low-grade Ovarian Serous Carcinoma. IJSBAR 2022;62(1):275-80.
37. Tu M, Gao X, Guo T, Lu W, Xu J. Clinicopathological and prognostic factor analyses of primary fallopian tube carcinoma and high-grade serous ovarian cancer. World J Surg Oncol 2025;23(1):1-10.
38. Wu NYY, Fang C, Huang HS, Wang J, Chu TY. Natural history of ovarian high-grade serous carcinoma from time effects of ovulation inhibition and progesterone clearance of p53-defective lesions. Mod Pathol 2020;33(1):29-37.
39. Zhang M, Cheng S, Jin Y, Zhao Y, Wang Y. Roles of CA125 in diagnosis, prediction, and oncogenesis of ovarian cancer. Biochim Biophys Acta - Rev Cancer 2021;1875(2):1-11.
40. Zhao H, Wang J, Zhang Y, Yuan M, Yang S, Lisong L, et al. Prognostic values of CCNE1 amplification and overexpression in cancer patients: A systematic review and meta-analysis. J Cancer 2018;9(13):2397-407.
