Iranian Journal of Pathology

Correlation of Before and After Invasive Breast Cancer Neoadjuvant Chemotherapy for NFkB, Cyclin D1, and Survivin Expression

Document Type : Original Research

Authors

Primariadewi Rustamadji 1
Elvan Wiyarta 2
Ineke Anggreani 3

1 Department of Anatomic Pathology, Faculty of Medicine Universitas Indonesia-Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia

2 Department of Medical Sciences, Faculty of Medicine Universitas Indonesia-Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia

3 Department of Anatomic Pathology, Faculty of Medicine Universitas Indonesia, Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia

https://doi.org/10.30699/ijp.2023.562935.2983
Abstract
Background & Objective: Patients undergoing neoadjuvant chemotherapy (NC) for invasive breast cancer (IBC) therapy need biomarkers to track their progress. Because of the relationship between NFkB, Survivin, and Cyclin D1 with NC resistance, the different expression levels of each of these biomarkers can be different between pre- and post-NC in IBC. However, no research has examined the correlation between these biomarkers before and after the NC expression. This study aimed to determine the correlation among them.
Methods: Biomarkers expression (low and high) was used to classify 30 samples. ER, PR, HER2, Ki-67 status, tumor grade, age, and NC response were assessed. The amounts of Survivin, Cyclin D1, and NFkB were evaluated using immunohistochemistry, and samples were classified based on the cut-off. Chi-square and linear regression were used to evaluate the data.
Results: No significant association was found with the changes in the expression of Survivin, Cyclin D1, and NFkB, both before and after the NC. Significant moderate correlations were shown between before and after the NC Survivin expression (r = 0.513) and Cyclin D1 expression (r = 0.543). The correlation between expression of NFkB before and after the NC was not significant.
Conclusion: The high potential of these proteins as prognostic indicators was demonstrated by the strong positive association between the expression of Survivin and Cyclin D1 before and after the NC. This upregulation of biomarkers indicates chemoresistance in developing IBC in the presence of NC.

Keywords

Breast cancer
Chemotherapy
Cyclin D1
Invasive
NFkB
Prognosis
Survivin

Subjects

  1. Estimated cancer incidence, mortality and prevalence in 2020: International Agency for Research on Cancer-WHO; 2020 [updated 2020/03/. Available from: https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf.
  2. Sharma GN, Dave R, Sanadya J, Sharma P, Sharma KK. Various types and management of breast cancer: an overview. J Adv Pharm Technol Res. 2010;1 (2):109-26.
  3. Rustamadji P, Wiyarta E, Bethania KA, Kusmardi K. Potential of AKT2 expression as a predictor of lymph-node metastasis in invasive breast carcinoma of no special type. J Pathol Transl Med. 2021;55 (4):271-8. [DOI:10.4132/jptm.2021.04.26] [PMID] [PMCID]
  4. Rustamadji P, Wiyarta E, Bethania KA. CD44 Variant Exon 6 Isoform Expression as a Potential Predictor of Lymph Node Metastasis in Invasive Breast Carcinoma of No Special Type. Int J Breast Cancer. 2021;2021:1586367. [DOI:10.1155/2021/1586367] [PMID] [PMCID]
  5. Lee A, Lim W, Moon BI, Paik NS, Koh SH, Song JY. Chemotherapy response assay test and prognosis for breast cancer patients who have undergone anthracycline- and taxane-based chemotherapy. J Breast Cancer. 2011;14 (4):283-8. [DOI:10.4048/jbc.2011.14.4.283] [PMID] [PMCID]
  6. Biliran H, Jr., Wang Y, Banerjee S, Xu H, Heng H, Thakur A, et al. Overexpression of cyclin D1 promotes tumor cell growth and confers resistance to cisplatin-mediated apoptosis in an elastase-myc transgene-expressing pancreatic tumor cell line. Clin Cancer Res. 2005;11 (16):6075-86. [DOI:10.1158/1078-0432.CCR-04-2419] [PMID]
  7. Garg H, Suri P, Gupta JC, Talwar GP, Dubey S. Survivin: a unique target for tumor therapy. Cancer Cell Int. 2016;16:49. [DOI:10.1186/s12935-016-0326-1] [PMID] [PMCID]
  8. Pacifico F, Leonardi A. NF-kappaB in solid tumors. Biochem Pharmacol. 2006;72 (9):1142-52. [DOI:10.1016/j.bcp.2006.07.032] [PMID]
  9. Chen X, Duan N, Zhang C, Zhang W. Survivin and Tumorigenesis: Molecular Mechanisms and Therapeutic Strategies. J Cancer. 2016;7 (3):314-23. [DOI:10.7150/jca.13332] [PMID] [PMCID]
  10. Rustamadji P, Wiyarta E, Anggreani I. Exploring the Expression of Survivin on Neoadjuvant Chemotherapy in Invasive Breast Carcinoma. Open Access Macedonian Journal of Medical Sciences. 2022;10 (B):1440-5. [DOI:10.3889/oamjms.2022.9940]
  11. Prisack HB, Karreman C Fau - Modlich O, Modlich O Fau - Audretsch W, Audretsch W Fau - Danae M, Danae M Fau - Rezai M, Rezai M Fau - Bojar H, et al. Predictive biological markers for response of invasive breast cancer to anthracycline/cyclophosphamide-based primary(radio-)chemotherapy.(0250-7005(Print)).
  12. Caparica R, Lambertini MA-O, Pondé N, Fumagalli D, de Azambuja E, Piccart M. Post-neoadjuvant treatment and the management of residual disease in breast cancer: state of the art and perspectives.(1758-8340(Print)).
  13. Rickham PP. HUMAN EXPERIMENTATION. CODE OF ETHICS OF THE WORLD MEDICAL ASSOCIATION. DECLARATION OF HELSINKI. Br Med J. 1964;2 (5402):177. [DOI:10.1136/bmj.2.5402.177] [PMID] [PMCID]
  14. Kusmardi K, Wiyarta E, Estuningtyas A, Sahar N, Midoen YH, Tedjo A. Potential of Phaleria macrocarpa Leaves Ethanol Extract to Upregulate the Expression of Caspase-3 in Mouse Distal Colon after Dextran Sodium Sulphate Induction. Pharmacognosy Journal. 2021;13:23-9. [DOI:10.5530/pj.2021.13.4]
  15. Kusmardi K, Wiyarta E, Estuningtyas A, Sahar N, Midoen YH, Tedjo A, et al. Potential Inhibition by Phaleria macrocarpa Leaves Ethanol Extract on Ki-67 Expression in Distal Colon Mouse. Pharmacognosy Journal. 2021;13:443-9. [DOI:10.5530/pj.2021.13.56]
  16. Rustamadji P, Wiyarta E, Bethania KA, Kusmardi K. Potential of AKT2 expression as a predictor of lymph-node metastasis in invasive breast carcinoma of no special type. J Pathol Transl Med. 2021;0 (0). [DOI:10.4132/jptm.2021.04.26] [PMID] [PMCID]
  17. Hashimoto K, Tsuda H, Koizumi F, Shimizu C, Yonemori K, Ando M, et al. Activated PI3K/AKT and MAPK pathways are potential good prognostic markers in node-positive, triple-negative breast cancer. Annals of Oncology. 2014;25 (10):1973-9. [DOI:10.1093/annonc/mdu247] [PMID]
  18. Kusmardi K, Wiyarta E, Rusdi NK, Maulana AM, Estuningtyas A, Sunaryo H. The potential of lunasin extract for the prevention of breast cancer progression by upregulating E-Cadherin and inhibiting ICAM-1. F1000Res. 2021;10:902. [DOI:10.12688/f1000research.55385.1] [PMID] [PMCID]
  19. Fusté NP, Castelblanco E, Felip I, Santacana M, Fernández-Hernández R, Gatius S, et al. Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer. Oncotarget. 2016;7 (19):26979-91. [DOI:10.18632/oncotarget.8876] [PMID] [PMCID]
  20. O'Brien J, Hayder H, Peng C. Automated Quantification and Analysis of Cell Counting Procedures Using ImageJ Plugins. JoVE. 2016 (117):e54719. [DOI:10.3791/54719-v] [PMID] [PMCID]
  21. Choudhury KR, Yagle KJ, Swanson PE, Krohn KA, Rajendran JG. A Robust Automated Measure of Average Antibody Staining in Immunohistochemistry Images. J Histochem Cytochem. 2010;58 (2):95-107. [DOI:10.1369/jhc.2009.953554] [PMID] [PMCID]
  22. Oparina NA-O, Erlandsson MA-O, Fäldt Beding AA-O, Parris TA-O, Helou K, Karlsson PA-O, et al. Prognostic Significance of BIRC5/Survivin in Breast Cancer: Results from Three Independent Cohorts. LID - 10.3390/cancers13092209 [doi] LID - 2209.(2072-6694(Print)). [DOI:10.3390/cancers13092209] [PMID] [PMCID]
  23. Rauch A, Carlstedt A, Emmerich C, Mustafa AM, Göder A, Knauer SK, et al. Survivin antagonizes chemotherapy-induced cell death of colorectal cancer cells.(1949-2553(Electronic)).
  24. Schäfer C, Göder A, Beyer M, Kiweler N, Mahendrarajah N, Rauch A, et al. Class I histone deacetylases regulate p53/NF-κB crosstalk in cancer cells.(1873-3913(Electronic)).
  25. Schneider G, Henrich A Fau - Greiner G, Greiner G Fau - Wolf V, Wolf V Fau - Lovas A, Lovas A Fau - Wieczorek M, Wieczorek M Fau - Wagner T, et al. Cross talk between stimulated NF-kappaB and the tumor suppressor p53.(1476-5594(Electronic)).
  26. Schneider G, Krämer OH. NFκB/p53 crosstalk-a promising new therapeutic target.(0006-3002(Print)).
  27. O'Connor DS, Wall Nr Fau - Porter ACG, Porter Ac Fau - Altieri DC, Altieri DC. A p34 (cdc2) survival checkpoint in cancer.(1535-6108(Print)). [DOI:10.1016/S1535-6108(02)00084-3] [PMID]
  28. Zhang Y, Yan H, Li R, Guo Y, Zheng R. High expression of survivin predicts poor prognosis in cervical squamous cell carcinoma treated with paclitaxel and carboplatin.(1536-5964(Electronic)).
  29. Virrey JJ, Guan S Fau - Li W, Li W Fau - Schönthal AH, Schönthal Ah Fau - Chen TC, Chen Tc Fau - Hofman FM, Hofman FM. Increased survivin expression confers chemoresistance to tumor-associated endothelial cells.(1525-2191(Electronic)).
  30. Cahyanur R, Irawan C. Cyclin D1 and Chemotherapy Response. Indonesian Journal of Cancer. 2021;15:41. [DOI:10.33371/ijoc.v15i1.782]
  31. Irawan C, Cahyanur R Fau - Lisnawati L, Lisnawati L Fau - Abdullah M, Abdullah M Fau - Yunus RE, Yunus RE. The Difference in the Cyclin D1 Expression in Advanced Stage Nasopharyngeal Cancer based on Treatment Response: A Retrospective Cohort Study.(0125-9326(Print)).
  32. Feng Z, Guo W Fau - Zhang C, Zhang C Fau - Xu Q, Xu Q Fau - Zhang P, Zhang P Fau - Sun J, Sun J Fau - Zhu H, et al. CCND1 as a predictive biomarker of neoadjuvant chemotherapy in patients with locally advanced head and neck squamous cell carcinoma.(1932-6203(Electronic)).
  33. Bradford CR, Kumar B Fau - Bellile E, Bellile E Fau - Lee J, Lee J Fau - Taylor J, Taylor J Fau - D'Silva N, D'Silva N Fau - Cordell K, et al. Biomarkers in advanced larynx cancer.(1531-4995(Electronic)).
  34. Galante JM, Mortenson MM, Schlieman MG, Virudachalam S, Bold RJ. Targeting NF-kB/BCL-2 pathway increases apoptotic susceptibility to chemotherapy in pancreatic cancer. Journal of Surgical Research. 2004;121 (2):306-7. [DOI:10.1016/j.jss.2004.07.130]

35. Godwin P, Baird Am Fau - Heavey S, Heavey S Fau - Barr MP, Barr Mp Fau - O'Byrne KJ, O'Byrne Kj Fau - Gately K, Gately K. Targeting nuclear factor-kappa B to overcome resistance to chemotherapy.(2234-943X(Print))

Iranian Journal of Pathology
Volume 18, Issue 2
Spring 2023
Pages 156-164

  • Receive Date 03 October 2022
  • Revise Date 15 January 2023
  • Accept Date 20 March 2023

Home

Guide for Authors

Submit Manuscript

Contact Us