J Breast Cancer.  2006 Jun;9(2):98-104. 10.4048/jbc.2006.9.2.98.

Expression of Interferon Regulatory Factors in Breast Cancer Tissue

• Yoon JH
• Park MH
• Cho MH
• Jaegal YJ
• Park CS

• KMID: 2286626
• DOI: http://doi.org/10.4048/jbc.2006.9.2.98

Abstract

PURPOSE
As neoplasia is the result of unbalanced cell growth and cell death, alternations in the growth control pathway including the immunity within the individual host-tumor relationship has been attributed to the development of breast cancer. Interferon(IFN)-gamma based immunity was recently reported to have an antitumor effect and some new methods to assess the state of interferon-gamma based immunity have been introduced. Interferon regulatory factor(IRF)-1 and interferon regulatory factor(IRF)-2 are transcriptional factors that mediate the effects of Interferon-gamma. It was suggested that the loss of IRF-1 expression is associated with the loss of tumor suppression and the development of IRF-2 expression is associated with oncogenic activation. Thus, we studied the significances of the IRF-1 and IRF-2 expressions as they are related with some clinicopathological parameters to determine the biological behavior of breast cancer including the menopausal status, tumor size, lymph node status, histologic grade, the expression of steroid receptors, the expression of c-erb B2 oncoprotein and the expression of p53 protein.
METHODS
Formalin-fixed paraffin embedded specimens from 82 patients with invasive ductal carcinoma were used to evaluate the expression of IRF-1 and IRF-2 by performing immunohistochemical staining with using an avidin-biotin-peroxidase complex technique.
RESULTS
The expression of IRF-1 was observed in 80.5 % of the study group. However, the expression of IRF-1 did not show any correlation with menopausal status, tumor size, histologic grade, the expression of steroid receptors, the expression of c-erb B2 oncoprotein and the p53 expression. Only lymph node metastasis showed a decreasing tendency of IRF-1 expression, but this was without statistical significance (p=0.075). The expression of IRF-2 was observed in 58.5% of the study group and it did not show any significant relationship with any of the above mentioned clinicopathological parameters.
CONCLUSION
This study suggests that the expression of IRF-1 and IRF-2 does not affect the previously established parameters for determining such biological behaviors of breast cancer as the tumor size, lymph node metastasis, the histologic grade, the expression of steroid receptors, the expression of c-erb B2 and the expression of p53. In spite of these results, We'd like to recommend that another study be done to evaluate the role of IRF-1 and IRF-2 for the proper selection of the patients who are suitable for immunotherapy.

Keyword

Breast cancer; Interferon regulatory factor; Clinicopathologic parameters

MeSH Terms

Breast Neoplasms*
Breast*
Carcinoma, Ductal
Cell Death
Humans
Immunotherapy
Interferon Regulatory Factors*
Interferon-gamma
Interferons*
Lymph Nodes
Neoplasm Metastasis
Paraffin
Receptors, Steroid
Interferon Regulatory Factors
Interferon-gamma
Interferons
Paraffin
Receptors, Steroid

Reference

1. Beatty GL, Paterson Y. Regulation of tumor growth by IFN-gamma in cancer immunotherapy. Immunologic Res. 2001. 24:201–210.

2. Mizokami MM, Hu P, Khawli LA, Li J, Epstein AL. Chimeric TNT-3 antibody/murine Interferon-gamma fusion protein for the immunotherapy of solid malignancies. Hybrid Hybridomics. 2003. 22:197–207.

3. Dummer R, Hassel JC, Fellenberg F, Eichmuller S, Maier T, Bleuzen P, et al. Adenovirus-mediated intralesional interferon-gamma gene transfer induces tumor regressions in cutaneous lymphomas. Blood. 2004. 104:1631–1638.

4. Khorana AA, Rosenblatt JD, Sahasrabudhe DM, Evans T, Ladrigan M, Marquis D, et al. A phase 1 trial of immunotherapy with intratumoral adenovirus-interferon-gamma (TG1041) in patients with malignant melanoma. Cancer Gene Ther. 2003. 10:251–259.

5. Doherty GM, Boucher L, Sorenson K, Lowney J. Interferon regulatory factor expression in human breast cancer. Ann Surg. 2001. 233:623–629.

6. Hadden JW. The immunology and immunotherapy of breast cnacer : an update. Int J Immunopharmacol. 1999. 21:79–101.

7. Barth RJ Jr, Mule JJ, Spiess PJ, Rosenberg SA. Interferon-gamma and tumor necrosis factor have a role in tumor regressions mediated by murine CD8+ tumor infiltrating lymphocytes. J Exp Med. 1991. 173:647–658.

8. Doherty GM, Alexander HR, Merino MJ, Venzon DJ, Norton JA. Role of endogenous interferon gamma in murine tumor growth and tumor necrosis factor alpha antitumor efficacy. Ann Surg Oncol. 1996. 3:198–203.

9. Doherty GM, Tsung K, McCluskey B, Norton JA. Endogenous interferon-γ acts directly on tumor cells in vivo to suppress growth. J Surg Res. 1996. 64:68–74.

10. Dighe AS, Richards E, Old LJ, Schreiber RD. Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity. 1994. 1:447–456.

11. Bezwoda WR, Meyer K. Effect of alpha-interferon, 17 beta-estradiol, and tamoxifen on estrogen receptor concentration and cell cycle kinetics of MCF 7 cells. Cancer Res. 1990. 50:5387–5391.

12. Kornek G, Reiner A, Sagaster P, Stierer M, Mayer A, Ludwig H. Effect of interferon alpha-2a on hormone receptor status in patients with advanced breast cancer. Cancer Invest. 1999. 17:189–194.

13. Nagorsen D, Scheibenbogen C, Schaller G, Leigh B, Schmittel A, Letsch A, et al. Differences in T-cell immunity toward tumor-associated antigens in colorectal cancer and breast cancer patients. Int J Cancer. 2003. 105:221–225.

14. Feuerer M, Beckhove P, Bai L, Solomayer EF, Bastert G, Diel IJ, et al. Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow. Nat Med. 2001. 7:452–458.

15. Kim PK, Armstrong M, Liu Y, Yan P, Bucher B, Zuckerbraun BS, et al. IRF-1 expression induces apoptosis and inhibits tumor growth in mouse mammary cancer cells in vitro and in vivo. Oncogene. 2004. 23:1125–1135.

16. Tanaka N, Ishihara M, Kitagawa M, Harada H, Kimura T, Matsuyama T, et al. Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the tran-scription factor IRF-1. Cell. 1994. 77:829–839.

17. Tamura T, Ishihara M, Lamphier MS, Tanaka N, Oishi I, Alzawa S, et al. An IRF-1 dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes. Nature. 1995. 376:596–599.

18. Harada H, Kitagawa M, Tanaka N, Yamamoto H, Harada K, Ishihara M, et al. Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2. Science. 1993. 259:971–974.