Intracellular Fibronectin Expression in Invasive Breast Carcinoma: Is It Related to Significant Clinicopathological Prognostic Factors?

IRCMJ logo
PDF
HTML

Keywords

Breast Cancer
Immunohistochemistry
Prognostic Factors
Fibronectin

How to Cite

Mohammadizadeh F., & Heydari S. (2020). Intracellular Fibronectin Expression in Invasive Breast Carcinoma: Is It Related to Significant Clinicopathological Prognostic Factors?. Iranian Red Crescent Medical Journal, 22(4). Retrieved from https://ircmj.org/index.php/IRCMJ/article/view/389

Abstract

Background: Fibronectin plays a key role in the extracellular matrix. The expression of fibronectin and its impact on tumor behavior have been studied in several tumors such as breast carcinoma.

Objectives: We aimed at investigating the immunohistochemical expression of intracellular fibronectin in breast carcinoma and its relationship with significant clinicopathological factors.

Methods: This case-control study was conducted on 125 formalin-fixed and paraffin-embedded tissue blocks, including 50 invasive breast carcinomas (tumor group) and their adjacent normal tissue (tumor control group), and 25 normal control samples from mammoplasty (normal control group). The samples were obtained from the pathology archive of Alzahra Hospital, Isfahan, Iran, from 2016 to 2018. All the 125 samples were stained immunohistochemically by the fibronectin antibody. Intracellular fibronectin expression was then compared between the three groups. Moreover, the relationship between fibronectin expression and some clinicopathological factors was evaluated in the tumor group.

Results: Fibronectin staining intensity and extent showed no significant difference between the normal control and tumor control groups (P-Value = 0.65 and 0.065, respectively), while the tumor group showed a significant difference from both normal control and tumor control groups in fibronectin staining intensity (P-Value = 0.002 and < 0.001, respectively) and fibronectin staining extent (P-Value < 0.001). In addition, a significant relationship between fibronectin expression in tumor samples and fibronectin staining intensity and tumor grade was observed (P-Value = 0.01). However, fibronectin expression did not show any significant relationship with age, tumor size, tumor subtype, and lymph node status.

Conclusions: Intracellular fibronectin expression seems to be a tendency observed in some breast carcinomas. Normal breast tissue, whether adjacent to carcinoma or normal control, does not show such a tendency. Despite the significant relationship between fibronectin expression and carcinoma grade, fibronectin expression did not show any significant relationship with tumor size and lymph node status.

PDF
HTML

References

  1. Kumar P, Kadakol A, Shasthrula PK, Mundhe NA, Jamdade VS, Barua CC, et al. Curcumin as an adjuvant to breast cancer treatment. Anticancer Agents Med Chem. 2015;15(5):647-56. doi: 10.2174/1871520615666150101125918. [PubMed: 25553436].
  2. Mohammadizadeh F, Zarean M, Abbasi M. Association of Epstein-Barr virus with invasive breast carcinoma and its impact on well-known clinicopathologic parameters in Iranian women. Adv Biomed Res. 2014;3:141. doi: 10.4103/2277-9175.135158. [PubMed: 25161988]. [PubMed Central: PMC4139983].
  3. McPherson K, Steel CM, Dixon JM. ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ. 2000;321(7261):624-8. doi: 10.1136/bmj.321.7261.624. [PubMed: 10977847]. [PubMed Central: PMC1118507].
  4. Zhou Z, Qutaish M, Han Z, Schur RM, Liu Y, Wilson DL, et al. MRI detection of breast cancer micrometastases with a fibronectin-targeting contrast agent. Nat Commun. 2015;6:7984. doi: 10.1038/ncomms8984. [PubMed: 26264658]. [PubMed Central: PMC4557274].
  5. Shi K, Wang SL, Shen B, Yu FQ, Weng DF, Lin JH. Clinicopathological and prognostic values of fibronectin and integrin alphavbeta3 expression in primary osteosarcoma. World J Surg Oncol. 2019;17(1):23. doi: 10.1186/s12957-019-1566-z. [PubMed: 30691475]. [PubMed Central: PMC6350278].
  6. Xiao J, Yang W, Xu B, Zhu H, Zou J, Su C, et al. Expression of fibronectin in esophageal squamous cell carcinoma and its role in migration. BMC Cancer. 2018;18(1):976. doi: 10.1186/s12885-018-4850-3. [PubMed: 30314454]. [PubMed Central: PMC6186055].
  7. Liao YX, Zhang ZP, Zhao J, Liu JP. Effects of Fibronectin 1 on cell proliferation, senescence and apoptosis of human glioma cells through the PI3K/AKT signaling pathway. Cell Physiol Biochem. 2018;48(3):1382-96. doi: 10.1159/000492096. [PubMed: 30048971].
  8. Jiang K, Song X, Yang L, Li L, Wan Z, Sun X, et al. Enhanced antitumor and anti-metastasis efficacy against aggressive breast cancer with a fibronectin-targeting liposomal doxorubicin. J Control Release. 2018;271:21-30. doi: 10.1016/j.jconrel.2017.12.026. [PubMed: 29277681].
  9. Kaushik S, Pickup MW, Weaver VM. From transformation to metastasis: Deconstructing the extracellular matrix in breast cancer. Cancer Metastasis Rev. 2016;35(4):655-67. doi: 10.1007/s10555-016-9650-0. [PubMed: 27914000]. [PubMed Central: PMC5215979].
  10. Bae YK, Kim A, Kim MK, Choi JE, Kang SH, Lee SJ. Fibronectin expression in carcinoma cells correlates with tumor aggressiveness and poor clinical outcome in patients with invasive breast cancer. Hum Pathol. 2013;44(10):2028-37. doi: 10.1016/j.humpath.2013.03.006. [PubMed: 23684510].
  11. Rocha M, Arcanjo R, Lopes C, Carneiro M, Souza A, Bao S. Modulation of fibronectin and laminin expression by Rhodium (II) citrate-coated maghemite nanoparticles in mice bearing breast tumor. Sci Rep. 2017;7(1):17904. doi: 10.1038/s41598-017-18204-1. [PubMed: 29263369]. [PubMed Central: PMC5738373].
  12. Ioachim E, Charchanti A, Briasoulis E, Karavasilis V, Tsanou H, Arvanitis DL, et al. Immunohistochemical expression of extracellular matrix components tenascin, fibronectin, collagen type IV and laminin in breast cancer: their prognostic value and role in tumour invasion and progression. Eur J Cancer. 2002;38(18):2362-70. doi: 10.1016/s0959-8049(02)00210-1. [PubMed: 12460779].
  13. Insua-Rodriguez J, Oskarsson T. The extracellular matrix in breast cancer. Adv Drug Deliv Rev. 2016;97:41-55. doi: 10.1016/j.addr.2015.12.017. [PubMed: 26743193].
  14. You D, Jung SP, Jeong Y, Bae SY, Lee JE, Kim S. Fibronectin expression is upregulated by PI-3K/Akt activation in tamoxifen-resistant breast cancer cells. BMB Rep. 2017;50(12):615-20. doi: 10.5483/bmbrep.2017.50.12.096. [PubMed: 28855026]. [PubMed Central: PMC5749907].
  15. Wang K, Andresen Eguiluz RC, Wu F, Seo BR, Fischbach C, Gourdon D. Stiffening and unfolding of early deposited-fibronectin increase proangiogenic factor secretion by breast cancer-associated stromal cells. Biomaterials. 2015;54:63-71. doi: 10.1016/j.biomaterials.2015.03.019. [PubMed: 25907040]. [PubMed Central: PMC4659482].
  16. Li W, Liu Z, Zhao C, Zhai L. Binding of MMP-9-degraded fibronectin to beta6 integrin promotes invasion via the FAK-Src-related Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways in breast cancer. Oncol Rep. 2015;34(3):1345-52. doi: 10.3892/or.2015.4103. [PubMed: 26134759].
  17. Li CL, Yang D, Cao X, Wang F, Hong DY, Wang J, et al. Fibronectin induces epithelial-mesenchymal transition in human breast cancer MCF-7 cells via activation of calpain. Oncol Lett. 2017;13(5):3889-95. doi: 10.3892/ol.2017.5896. [PubMed: 28521486]. [PubMed Central: PMC5431265].
  18. Fernandez-Garcia B, Eiro N, Marin L, Gonzalez-Reyes S, Gonzalez LO, Lamelas ML, et al. Expression and prognostic significance of fibronectin and matrix metalloproteases in breast cancer metastasis. Histopathology. 2014;64(4):512-22. doi: 10.1111/his.12300. [PubMed: 24117661].
  19. Sun Y, Kim HS, Saw PE, Jon S, Moon WK. Targeted therapy for breast cancer stem cells by liposomal delivery of siRNA against fibronectin EDB. Adv Healthc Mater. 2015;4(11):1675-80. doi: 10.1002/adhm.201500190. [PubMed: 26097122].
  20. Femel J, Huijbers EJ, Saupe F, Cedervall J, Zhang L, Roswall P, et al. Therapeutic vaccination against fibronectin ED-A attenuates progression of metastatic breast cancer. Oncotarget. 2014;5(23):12418-27. doi: 10.18632/oncotarget.2628. [PubMed: 25360764]. [PubMed Central: PMC4322999].
  21. Wang JP, Hielscher A. Fibronectin: How its aberrant expression in tumors may improve therapeutic targeting. J Cancer. 2017;8(4):674-82. doi: 10.7150/jca.16901. [PubMed: 28367247]. [PubMed Central: PMC5370511].
  22. Christensen L, Nielsen M, Holund B, Clemmensen I. In vivo demonstration of cytoplasmic fibronectin in human breast carcinomas. Virchows Arch A Pathol Anat Histopathol. 1985;407(3):337-46. doi: 10.1007/bf00710658. [PubMed: 3929464].
  23. Vasaturo F, Sallusti E, Gradilone A, Malacrino C, Nardo T, Avagnano G, et al. Comparison of extracellular matrix and apoptotic markers between benign lesions and carcinomas in human breast. Int J Oncol. 2005;27(4):1005-11. [PubMed: 16142317].