Expression of Cyclin D1 and Claudin-1 in Invasive Breast Carcinoma and Their Correlation with Clinicopathological Parameters

Document Type : Original Research

Authors

1 Department of Pathology, SGT Medical College Hospital and Research Institute, SGT University, Gurugram, Haryana, India

2 Department of Pathology, Maharishi Markandeshwar Institute of Medical Sciences and Research, Maharishi Markandeshwar Deemed to be University, Mullana-Ambala, Haryana, India

Abstract
Background & Objective: Evidence-based medicine has shown that patients with similar risk factors, stages, and therapy often have different clinical outcomes, highlighting the heterogeneity of breast cancer. In a quest for a better, cost-effective approach, researchers proposed the selection of surrogate IHC markers such as cyclin D1 and claudin-1 for the prognosis of breast cancer patients, supplementing the traditional ER, PR, and HER2/neu receptor.
Methods: This retrospective study was conducted in a tertiary care hospital in northern India and included 50 cases of invasive breast carcinoma obtained from mastectomies, wide local excisions, and biopsies diagnosed over 4 years. In addition to ER, PR, and Her2/neu, claudin-1 and cyclin D1 IHC expression was assessed.
Results: Cyclin D1 expression exhibited a statistically significant correlation with nodal status involvement (P=0.011) and with luminal-type breast carcinoma (P=0.023). Though there was no significant statistical correlation between claudin-1 and various clinic pathological features, it was seen to be positive in both luminal and HER2/neu-positive tumors.
Conclusion: Our findings advocated the expression of IHC, namely, cyclin D1 and claudin-1, in cases of breast cancer. Cyclin D1 positivity may show a significant association with better prognostic determinants, while claudin-1 negative tumors may tend to be more often triple negative. Thus, IHC can be used in resource-constraint settings to substitute expensive molecular techniques.

Keywords

Subjects


  1. Sathishkumar K, Chaturvedi M, Das P, Stephen S, Mathur P. Cancer incidence estimates for 2022 & projection for 2025: results from National Cancer Registry Programme, India. Indian J Med Res. 2022;156(4-5):598-607. [DOI:10.4103/ijmr.ijmr_1821_22] [PMID] [PMCID]
  2. Malvia S, Bagadi SA, Dubey US, Saxena S. Epidemiology of breast cancer in Indian women. Asia Pac J Clin Oncol. 2017;13(4):289-95. [DOI:10.1111/ajco.12661] [PMID]
  3. Lakhani SR, Ellis IO, Schnitt SJ, Tan PJ, Van de Vijver MJ, editors. WHO Classification of Tumours of the Breast. Lyon: IARC; 2012.
  4. Polyak K. Heterogeneity in breast cancer. J Clin Invest. 2011;121(10):3786-8. [DOI:10.1172/JCI60534] [PMID] [PMCID]
  5. Wang M, Wu K, Zhang P, Zhang M, Ding A, Chen H. The prognostic significance of the Oncotype DX Recurrence Score in T 1-2 N 1 M 0 estrogen receptor-positive HER2-negative breast cancer based on the prognostic stage in the updated AJCC 8th edition. Ann Surg Oncol. 2019;26:1227-35. [DOI:10.1245/s10434-018-7068-3] [PMID]
  6. Gillett C, Fantl V, Smith R, et al. Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res. 1994;54(7):1812-7.
  7. Tobin NP, Sims AH, Lundgren KL, Lehn S, Landberg G. Cyclin D1, Id1 and EMT in breast cancer. BMC Cancer. 2011;11:417. [DOI:10.1186/1471-2407-11-417] [PMID] [PMCID]
  8. Ishii Y, Pirkmaier A, Alvarez JV, et al. Cyclin D1 overexpression and response to bortezomib treatment in a breast cancer model. J Natl Cancer Inst. 2006;98:1238-47. [DOI:10.1093/jnci/djj334] [PMID]
  9. Eeckhoute J, Carroll JS, Geistlinger TR, Torres-Arzayus MI, Brown M. A cell-type-specific transcriptional network required for estrogen regulation of cyclin D1 and cell cycle progression in breast cancer. Genes Dev. 2006;20:2513-26. [DOI:10.1101/gad.1446006] [PMID] [PMCID]
  10. Zhou B, Moodie A, Blanchard AA, Leygue E, Myal Y. Claudin-1 in breast cancer: new insights. J Clin Med. 2015;4(12):1960-76. [DOI:10.3390/jcm4121952] [PMID] [PMCID]
  11. Perou CM. Molecular stratification of triple-negative breast cancers. Oncologist. 2011;16(S1):61-70. [DOI:10.1634/theoncologist.2011-S1-61] [PMID]
  12. Dabbs DJ. Diagnostic Immunohistochemistry: Theranostic and Genomic Applications. 4th ed. Philadelphia (PA): Elsevier Saunders; 2014.
  13. Yang XR, Sherman ME, Rimm DL, et al. Differences in risk factors for breast cancer molecular subtypes in a population-based study. Cancer Epidemiol Biomarkers Prev. 2007;16(3):439-43. [DOI:10.1158/1055-9965.EPI-06-0806] [PMID]
  14. Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER) negative, progesterone receptor (PR) negative, and HER2 negative invasive breast cancer, the so-called triple negative phenotype. Cancer. 2007;109(9):1721-8. [DOI:10.1002/cncr.22618] [PMID]
  15. Asthana S, Labani PS, Labani S. A review on cancer incidence in India from 25 population-based cancer registries. J Dr NTR Univ Health Sci. 2015;4(3):150-4. [DOI:10.4103/2277-8632.165397]
  16. Mohammadizadeh F, Hani M, Ranaee M, Bagheri M. Role of cyclin D1 in breast carcinoma. J Res Med Sci. 2013;18(12):1021-5.
  17. Peurala E, Koivunen P, Haapasaari KM, Bloigu R, Jukkola-Vuorinen A. The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer. Breast Cancer Res. 2013;15(1):R5. [DOI:10.1186/bcr3376] [PMID] [PMCID]
  18. Ananthamurthy A, Ravikumar G. Cyclin D1 expression in ductal carcinoma of the breast and its correlation with other prognostic parameters. J Cancer Res. 2014;10(3):671-5. [DOI:10.4103/0973-1482.138135] [PMID]
  19. Knight WA III, Livingston RB, Gregory EJ, McGuire WL. Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. Cancer Res. 1977;37(12):4669-71.
  20. Clark GM, Osborne CK, McGuire WL. Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer. J Clin Oncol. 1984;2(10):1102-9. [DOI:10.1200/JCO.1984.2.10.1102] [PMID]
  21. Bhargava R, Dabbs DJ. Diagnostic Immunohistochemistry: Theranostic and Genomic Applications. 2019. Elsevier.
  22. Sandhu GS, Erqou S, Patterson H, Mathew A. Prevalence of triple-negative breast cancer in India: systematic review and meta-analysis. J Glob Oncol. 2016;2(6):412-21. [DOI:10.1200/JGO.2016.005397] [PMID] [PMCID]
  23. Ko BS, Kim HJ, Yu JH, et al. Claudin-1, -3, -4, and -7 expression in triple-negative breast cancer. J Clin Oncol. 2013;31(15):1070. [DOI:10.1200/jco.2013.31.15_suppl.1070]
  24. Prat A, Parker JS, Karginova O, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 2010;12(5):R68.
  25. Xu J, Lan KT, Su TH et al. Clinicopathologic and prognosis features of Claudin-low breast cancers. Zhonghua Bing Li Xue Za Zhi 2017; 46(9):634-639 [DOI:10.1186/bcr2635] [PMID] [PMCID]
  26. Lundberg A, Lindström LS, Li J, et al. The long-term prognostic and predictive capacity of cyclin D1 gene amplification in 2305 breast tumours. Breast Cancer Res. 2019;21(1):1-0. [DOI:10.1186/s13058-019-1121-4] [PMID] [PMCID]
  27. Mohammadizadeh F, Hani M, Ranaee M, Bagheri M. Role of cyclin D1 in breast carcinoma. J Res Med Sci. 2013;18(12):1021-5.
  28. Tőkés AM, Kulka J, Paku S, et al. Claudin-1, -3, and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study. Breast Cancer Res. 2005;7:1-0. [DOI:10.1186/bcr1265] [PMCID]
  29. Guo L, Liu S, Jakulin A, Yilamu D, Wang B, Yan J. Positive expression of cyclin D1 is an indicator for the evaluation of the prognosis of breast cancer. Int J Clin Exp Med. 2015;8(10):18656. [DOI:10.3892/etm.2015.2657] [PMID] [PMCID]
  30. Kucukzeybek BB, Bayoglu IV, Kucukzeybek Y, et al. The prognostic significance of cyclin D1 expression in patients with triple-negative breast cancer. J BUON. 2017;22(4):947-52.
  31. Blanchard AA, Ma X, Dueck KJ, et al. Claudin 1 expression in basal-like breast cancer is related to patient age. BMC Cancer. 2013;13:1-3. [DOI:10.1186/1471-2407-13-268] [PMID] [PMCID]
Volume 19, Issue 4
Autumn 2024
Pages 408-414

  • Receive Date 13 May 2024
  • Accept Date 10 June 2024