Histological marker of ovarian cancer prognostic characterization

Authors

  • I Made Egga Adika Suputra Faculty of Medicine, Universitas Udayana Author
  • I Putu Eka Widiadnyana Putra Faculty of Medicine, Universitas Udayana Author
  • I Gusti Kamasan Nyoman Arijana Department of Histology, Faculty of Medicine, Universitas Udayana Author
  • Putu Anda Tusta Adiputra Oncologic Surgery Subdivision, Department of Surgery, Faculty of Medicine, Universitas Udayana Author
  • I Gede Putu Supadmanaba Biochemistry Department, Faculty of Medicine, Universitas Udayana Author

Keywords:

Ovarian Cancer, CA-125, HE4, P53, BRCA1/2

Abstract

This review investigates the role of histological markers in the prognostic characterization of ovarian cancer, focusing on their potential to improve diagnosis, prognosis, and personalized treatment strategies. This paper was created using a literature review methodology with Boolean logic operators "AND" and "OR" with keywords such as "CA-125," "HE4," "P53," "BRCA1/2" "Ki-67," "WT1," "PD-L1," "VEGF," "FOLR1," "ovarian cancer," "histology pattern," "prognostic marker," and "comparative analysis". We use several databases including PubMed, Springer Nature, Google Scholar and ScienceDirect. The results emphasize the significance of molecular pathways, genetic mutations, and immune cell infiltration in the tumor microenvironment, highlighting the prognostic value of biomarkers like CA-125, HE4, p53, BRCA1/2, WT1, PD-L1, FOLR1, and VEGF . The study also emphasizes the need of several biomarkers to improve prognosis accuracy and direct personalized treatments. This review also found M2 macrophages and CD8+ T lymphocytes are immune to cancer activity and treatment results. The review implies that combining conventional and new biomarkers with cutting-edge technologies and single-cell transcriptomics could enhance early identification and focused treatments. Improving patient outcomes and survival rates in ovarian cancer.

Author Biographies

  • I Made Egga Adika Suputra, Faculty of Medicine, Universitas Udayana

    Faculty of Medicine, Universitas Udayana

  • I Putu Eka Widiadnyana Putra, Faculty of Medicine, Universitas Udayana

    Faculty of Medicine, Universitas Udayana

  • I Gusti Kamasan Nyoman Arijana, Department of Histology, Faculty of Medicine, Universitas Udayana

    Department of Histology, Faculty of Medicine, Universitas Udayana

  • Putu Anda Tusta Adiputra, Oncologic Surgery Subdivision, Department of Surgery, Faculty of Medicine, Universitas Udayana

    Oncologic Surgery Subdivision, Department of Surgery, Faculty of Medicine, Universitas Udayana

  • I Gede Putu Supadmanaba, Biochemistry Department, Faculty of Medicine, Universitas Udayana

    Biochemistry Department, Faculty of Medicine, Universitas Udayana

References

1. Sung H. , Ferlay J. , Siegel R. , Laversanne M. , Soerjomataram I. , Jemal A. et al.. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 2021;71(3):209-249. https://doi.org/10.3322/caac.21660

2. Qiu L. and Weng G.. The diagnostic value of serum mir-21 in patients with ovarian cancer: a systematic review and meta-analysis. Journal of Ovarian Research 2022;15(1). https://doi.org/10.1186/s13048-022-00985-3

3. Zhang N. , Yang Z. , Jin Y. , Cheng S. , Yang J. , & Wang Y.. Low expression of circular rna hsa_circ_0078607 predicts poor prognosis in high-grade serous ovarian cancer. 2020. https://doi.org/10.21203/rs.3.rs-121237/v1

4. Bhobe D. , Lang A. , Warren C. , & Hassadia A.. Mucinous borderline ovarian tumour with torsion and micro-invasion and associated with high serum level of carbohydrate antigen 19-9: a case report. Hong Kong Journal of Gynaecology, Obstetrics and Midwifery 2021;21(2):86-89. https://doi.org/10.12809/hkjgom.21.2.03

5. Wang Z. , Yang L. , Huang Z. , Li X. , Xiao J. , Qu Y. et al.. Identification of prognosis biomarkers for high-grade serous ovarian cancer based on stemness. Frontiers in Genetics 2022;13. https://doi.org/10.3389/fgene.2022.861954

6. Katoh K. , Katoh Y. , Kubo A. , Iida M. , Ikeda Y. , Iwata T. et al.. Serum free fatty acid changes caused by high expression of stearoyl-coa desaturase 1 in tumor tissues are early diagnostic markers for ovarian cancer. Cancer Research Communications 2023;3(9):1840-1852. https://doi.org/10.1158/2767-9764.crc-23-0138

7. Keskin S. and Altın D.. Predictor role of systemic inflammation in ovarian cancer. Middle Black Sea Journal of Health Science 2021;7(2):282-288. https://doi.org/10.19127/mbsjohs.984093

8. Cai J. , Qiu J. , Wang H. , Sun J. , & Ji Y.. Identification of potential biomarkers in ovarian carcinoma and an evaluation of their prognostic value. Annals of Translational Medicine 2021;9(18):1472-1472. https://doi.org/10.21037/atm-21-4606

9. Ye H. , Ding H. , & Zheng Q.. Single-cell transcriptomic construction of fibroblast score for analysis of immune infiltration in primary and metastatic ovarian cancer. 2024. https://doi.org/10.21203/rs.3.rs-4485189/v1

10. Engqvist H. , Parris T. , Kovács A. , Rönnerman E. , Sundfeldt K. , Karlsson P. et al.. Validation of novel prognostic biomarkers for early-stage clear-cell, endometrioid and mucinous ovarian carcinomas using immunohistochemistry. Frontiers in Oncology 2020;10. https://doi.org/10.3389/fonc.2020.00162

11. Sihombing U., Purwoto G., Gandamihardja S., Harahap A., Rustamadji P., Kekalih A.et al.. Expression of cd44+/cd24-, rad6 and ddb2 on chemotherapy response in ovarian cancer: a prospective flow cytometry study. Gynecologic Oncology Reports 2022;42:101005. https://doi.org/10.1016/j.gore.2022.101005

12. Sihombing U., Purwoto G., Gandamihardja S., Harahap A., Rustamadji P., Kekalih A.et al.. Expression of cd44+/cd24-, rad6 and ddb2 on chemotherapy response in ovarian cancer: a prospective flow cytometry study. Gynecologic Oncology Reports 2022;42:101005. https://doi.org/10.1016/j.gore.2022.101005

13. Kang K. , Koh E. , Jang J. , & Kim C.. Multiple biomarkers are more accurate than a combination of carbohydrate antigen 125 and human epididymis protein 4 for ovarian cancer screening. Obstetrics &Amp; Gynecology Science 2022;65(4):346-354. https://doi.org/10.5468/ogs.22017

14. Zahran A., Abu-Salih A., Al-Bdour M., Abu-Salih L., & Bani‐Hani K.. Cyclin e and p53: the dynamic duo in ovarian tumor pathogenesis. 2024. https://doi.org/10.21203/rs.3.rs-4130179/v1

15. Xu F, Li J, Ni M, Cheng J, Zhao H, Wang S, et al. Fbw7 suppresses ovarian cancer development by targeting the n6-methyladenosine binding protein YTHDF2. Mol Cancer. 2021;20(1). doi:10.1186/s12943-021-01340-8.

16. Cai Y, Hu Y, Yu F, Tong W, Wang S, Sheng S, et al. Ahnak suppresses ovarian cancer progression through the Wnt/β-catenin signaling pathway. Aging (Albany NY). 2021;13(20):23579-87. doi:10.18632/aging.203473.

17. Guo J., Feng H., & Gu X.. Association between benign ovarian tumors and ovarian cancer risk: a meta-analysis of ten epidemiological studies. Frontiers in Oncology 2022;12. https://doi.org/10.3389/fonc.2022.895618

18. Jie Y., Li J., Man C., & Fan Y.. Ovarian cancer with intestinal wall invasion and hyperamylasemia: a case report. Frontiers in Oncology 2024;14. https://doi.org/10.3389/fonc.2024.1299226

19. Boylan K., Afiuni‐Zadeh S., Geller M., Argenta P., Griffin T., & Skubitz A.. Evaluation of the potential of pap test fluid and cervical swabs to serve as clinical diagnostic biospecimens for the detection of ovarian cancer by mass spectrometry-based proteomics. Clinical Proteomics 2021;18(1). https://doi.org/10.1186/s12014-020-09309-3

20. Kang K., Koh E., Jang J., & Kim C.. Multiple biomarkers are more accurate than a combination of carbohydrate antigen 125 and human epididymis protein 4 for ovarian cancer screening. Obstetrics & Gynecology Science 2022;65(4):346-354. https://doi.org/10.5468/ogs.22017

21. Xu J., Shen Y., Wang C., Tang S., Hong S., Lü W.et al.. Arsenic compound sensitizes homologous recombination proficient ovarian cancer to parp inhibitors. Cell Death Discovery 2021;7(1). https://doi.org/10.1038/s41420-021-00638-2

22. Sun W., Li J., Zhang Z., & Su X.. Gastrointestinal events with parp inhibitors in cancer patients: a meta‐analysis of phase ii/iii randomized controlled trials. Journal of Clinical Pharmacy and Therapeutics 2020;46(2):241-255. https://doi.org/10.1111/jcpt.13300

23. Monk B., Parkinson C., Lim M., O’Malley D., Oaknin A., Wilson M.et al.. A randomized, phase iii trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (athena–mono/gog-3020/engot-ov45). Journal of Clinical Oncology 2022;40(34):3952-3964. https://doi.org/10.1200/jco.22.01003

24. Zhai, Y., Lu, Q., Lou, T., Cao, G., Wang, S., & Zhang, Z. (2020). Muc16 affects the biological functions of ovarian cancer cells and induces an antitumor immune response by activating dendritic cells. Annals of Translational Medicine, 8(22), 1494-1494. https://doi.org/10.21037/atm-20-6388

25. Zhai, Y., Lu, Q., Lou, T., Cao, G., Wang, S., & Zhang, Z. (2020). Muc16 affects the biological functions of ovarian cancer cells and induces an antitumor immune response by activating dendritic cells. Annals of Translational Medicine, 8(22), 1494-1494. https://doi.org/10.21037/atm-20-6388

26. Wu, Y., Liu, Q., Xie, Y., Zhu, J., Zhang, S., Ge, Y., & Cheng, Z. (2023). Muc16 stimulates neutrophils to an inflammatory and immunosuppressive phenotype in ovarian cancer. Journal of Ovarian Research, 16(1). https://doi.org/10.1186/s13048-023-01207-0

27. Shipp A, Torres W. An incidental fallopian tube focal serous tubal intraepithelial lesion (STIL) discovered on a postoperative pathology report following hysterectomy and salpingectomy: a case report. Cureus. 2024. doi: 10.7759/cureus.60992.

28. Khiste S, Liu Z, Roy K, Uddin M, Hosain S, Gu X, et al. Ceramide–rubusoside nanomicelles, a potential therapeutic approach to target cancers carrying p53 missense mutations. Mol Cancer Ther. 2020;19(2):564-74. doi: 10.1158/1535-7163.MCT-19-0366.

29. Guo M, Qiao Y, Lu Y, Zhu L, Zheng L. Squalene epoxidase facilitates cervical cancer progression by modulating tumor protein p53 signaling pathway. J Obstet Gynaecol Res. 2023;49(5):1383-92. doi: 10.1111/jog.15576.

30. Neal A, Lai T, Singh T, Rahseparian N, Grogan T, Elashoff D, et al. Combining REACp53 with carboplatin to target high-grade serous ovarian cancers. Cancers (Basel). 2021;13(23):5908. doi: 10.3390/cancers13235908.

31. Mohapatra, I., Harshini, N., Samantaray, S., & Sahitya, K. (2021). Immunohistochemical expression of p53 and ki-67 on epithelial tumors of ovary. International Journal of Reproduction Contraception Obstetrics and Gynecology, 10(3), 1005. https://doi.org/10.18203/2320-1770.ijrcog20210724

32. Mielczarek‐Palacz, A., Sikora, J., Kondera‐Anasz, Z., Smycz‐Kubańska, M., Englisz, A., Strzelczyk, J., … & Kabut, J. (2020). The immune complex p53 protein/anti-p53 autoantibodies in the pathogenesis of ovarian serous carcinoma. Ginekologia Polska, 91(9), 519-253. https://doi.org/10.5603/gp.a2020.0123

33. Iwahashi, N., Ikezaki, M., Nishikawa, T., Namba, N., Ohgita, T., Saito, H., … & Nishitsuji, K. (2020). Sulfated glycosaminoglycans mediate prion-like behavior of p53 aggregates. Proceedings of the National Academy of Sciences, 117(52), 33225-33234. https://doi.org/10.1073/pnas.2009931117

34. Zhai Y, Lu Q, Lou T, Cao G, Wang S, Zhang Z. MUC16 affects the biological functions of ovarian cancer cells and induces an antitumor immune response by activating dendritic cells. Ann Transl Med. 2020;8(22):1494. doi: 10.21037/atm-20-6388.

35. Rabban, J., Garg, K., Ladwig, N., Zaloudek, C., & Devine, W. (2021). Cytoplasmic pattern p53 immunoexpression in pelvic and endometrial carcinomas with tp53 mutation involving nuclear localization domains. The American Journal of Surgical Pathology, 45(11), 1441-1451. https://doi.org/10.1097/pas.0000000000001713

36. Yue W, Ma J, Xiao Y, Wang P, Gu X, Xie B, et al. The apoptotic resistance of BRCA1-deficient ovarian cancer cells is mediated by cAMP. Front Cell Dev Biol. 2022. doi: 10.3389/fcell.2022.889656.

37. Akahane T, Masuda K, Hirasawa A, Kobayashi Y, Ueki A, Kawaida M, et al. TP53 variants in p53 signatures and the clonality of STICs in RRSO samples. J Gynecol Oncol. 2022;33(4). doi: 10.3802/jgo.2022.33.e50.

38. Gregory-Davis K, Walker A, Colello L, McKinnon W, Everett E, Chang M. Serous tubal intraepithelial carcinoma in a risk-reducing salpingo-oophorectomy specimen from a RAD51D mutation carrier: a case report. Int J Gynecol Pathol. 2022;42(1):89-92. doi: 10.1097/PGP.0000000000000857.

39. Paracchini L, Pesenti C, Marchette M, Beltrame L, Bianchi T, Grassi T, et al. Detection of TP53 clonal variants in Papanicolaou test samples collected up to 6 years prior to high-grade serous epithelial ovarian cancer diagnosis. JAMA Netw Open. 2020;3(7):e207566. doi: 10.1001/jamanetworkopen.2020.7566.

40. Faust J, Hamill D, Kolb E, Gopalakrishnapillai A, Barwe S. Mesothelin: an immunotherapeutic target beyond solid tumors. Cancers (Basel). 2022;14(6):1550. doi: 10.3390/cancers14061550.

41. Huo, Q., Xu, C., Shao, Y., Qin, Y., Huang, L., Liu, Y., … & Bao, H. (2021). Free ca125 promotes ovarian cancer cell migration and tumor metastasis by binding mesothelin to reduce dkk1 expression and activate the sgk3/foxo3 pathway. International Journal of Biological Sciences, 17(2), 574-588. https://doi.org/10.7150/ijbs.52097

42. Su, D., Nie, M., & Yue, J. (2021). The g199x and v157fs mutations in the tp53 gene promote malignancy in serous ovarian cancer: an analysis using whole-exome sequencing. Annals of Translational Medicine, 9(8), 710-710. https://doi.org/10.21037/atm-21-583

43. Singh N, Piskorz A, Bosse T, Jimenez-Liñan M, Rous B, Brenton J, et al. P53 immunohistochemistry is an accurate surrogate for TP53 mutational analysis in endometrial carcinoma biopsies. J Pathol. 2020;250(3):336-45. doi: 10.1002/path.5375.

44. Boylan, K., Afiuni‐Zadeh, S., Geller, M., Argenta, P., Griffin, T., & Skubitz, A. (2021). Evaluation of the potential of pap test fluid and cervical swabs to serve as clinical diagnostic biospecimens for the detection of ovarian cancer by mass spectrometry-based proteomics. Clinical Proteomics, 18(1). https://doi.org/10.1186/s12014-020-09309-3

45. Zhao, X. and He, M. (2020). Comprehensive pathway-related genes signature for prognosis and recurrence of ovarian cancer. Peerj, 8, e10437. https://doi.org/10.7717/peerj.10437

46. Kang, K., Koh, E., Jang, J., & Kim, C. (2022). Multiple biomarkers are more accurate than a combination of carbohydrate antigen 125 and human epididymis protein 4 for ovarian cancer screening. Obstetrics & Gynecology Science, 65(4), 346-354. https://doi.org/10.5468/ogs.22017

47. Zhang, N., Yang, Z., Jin, Y., Cheng, S., Yang, J., & Wang, Y. (2020). Low expression of circular rna hsa_circ_0078607 predicts poor prognosis in high-grade serous ovarian cancer.. https://doi.org/10.21203/rs.3.rs-121237/v1

48. Li, Q., Xiao, X., Feng, J., Yan, R., & Xi, J. (2023). Machine learning-assisted analysis of epithelial mesenchymal transition pathway for prognostic stratification and immune infiltration assessment in ovarian cancer. Frontiers in Endocrinology, 14. https://doi.org/10.3389/fendo.2023.1196094

49. Gao P, Peng T, Cao C, Lin S, Wu P, Huang X, et al. Association of CLDN6 and CLDN10 with immune microenvironment in ovarian cancer: a study of the claudin family. Front Genet. 2021;12:595436. doi: 10.3389/fgene.2021.595436.

50. Lan Y, Ding Y, Wan T, Deng T, Huang H, Liu J. Significance of CD47 and its association with tumor immune microenvironment heterogeneity in ovarian cancer. Front Immunol. 2021;12:768115. doi: 10.3389/fimmu.2021.768115.

51. Wei, Y., Ou, T., Lu, Y., Wu, G., Long, Y., Pan, X., … & Yao, D. (2020). Peer review #2 of "classification of ovarian cancer associated with brca1 mutations, immune checkpoints, and tumor microenvironment based on immunogenomic profiling (v0.2)".. https://doi.org/10.7287/peerj.10414v0.2/reviews/2

52. Wang, Y., Ding, M., Yuan, X., Ruibao, J., Zhu, D., Huang, W., … & Liu, Y. (2021). Lncrna snhg15 promotes ovarian cancer progression through regulated cdk6 via sponging mir‐370‐3p. Biomed Research International, 2021(1). https://doi.org/10.1155/2021/9394563

53. Yang, M., Chen, G., Gao, K., & Wang, Y. (2021). Tumor immunometabolism characterization in ovarian cancer with prognostic and therapeutic implications. Frontiers in Oncology, 11. https://doi.org/10.3389/fonc.2021.622752

54. Xiong, J., Chen, J., Sun, X., Zhao, R., & Gao, K. (2023). Prognostic role of long non-coding rna usp30-as1 in ovarian cancer: insights into immune cell infiltration in the tumor microenvironment. Aging, 15(23), 13776-13798. https://doi.org/10.18632/aging.205262

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Published

2025-02-16

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Vol. 1 No. 1 (2025)

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REVIEW