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Immunohistochemical Expression of Fn14 in invasive Ductal Carcinoma (IDC) and its Correlation with Clinical and Histopathological parameters of Human Breast cancer

Author Affiliations

  • 1 Dept. of Histochemistry and Cell Biology, Medical Research Institute, Al Ibrahimeyah, Alexandria University, Alexandria, EGYPT
  • 2 Dept. of Pathology, Medical Research Institute, Al Ibrahimeyah, Alexandria University, Alexandria, EGYPT

Int. Res. J. Medical Sci., Volume 3, Issue (2), Pages 7-15, February,28 (2015)


Fibroblast growth factor-inducible 14 (Fn14), is a member of the tumor necrosis factor receptor superfamily that normally expressed in healthy tissues, but its expression is increased in injured tissue where it thought to play role in tissue remodeling. Over expression of Fn14 expression is reported in many tumors, which is why this protein is under consideration as a therapeutic target in oncology.The aim of the present work was to investigate the expression of Fn14 as a novel prognostic biomarker in human invasive ductal carcinoma (IDC) versus benign tumors and normal breast tissues as well as their correlation with different pathological and histological parameters. Immunohistochemical technique was used to examine the expression of Fn14 in normal, benign as well as in IDC. Present results showed higher expression of Fn14 in IDC comparing to normal and benign breast tissues. Statistical analysis showed significant correlations between the expression of Fn14 and histological tumor grade, lymph node metastasis (LNM) and HER2/neu. Negative correlation was noticed between the expression of Fn14 and both ER and PR status. Current results suggest that Fn14 protein may be a valuable prognostic and therapeutic marker inhuman IDC pateints.


  1. DeSantis C., Ma J., Bryan L., and Jemal A., Breast cancer statistics, 2013, CA Cancer J. Clin.,64(1), 52-62 (2014)
  2. Jemal A., Bray F., Center M.M., Ferlay J., Ward E. and Forman D., Global cancer statistics, CA Cancer J. Clin.,61(2), 69-90 (2011)
  3. Lehner J., Stötzer O.J., Fersching D., Nagel D. and Holdenrieder S., Circulating plasma DNA and DNA integrity in breast cancer patients undergoing neoadjuvantchemotherapy, Clin. Chim. Acta., 425, 206-11 (2013)
  4. Shulman L.N., Willett W., Sievers A. and Knaul F.M., Breast cancer in developing countries: opportunities for improved survival., J. Oncol., 595167 (2010)
  5. Wiley S.R., Cassiano L., Lofton T., Davis-Smith T., Winkles J.A. and Lindner V.A. et al., A novel TNF receptor family member binds TWEAK and is implicated in an angiogenesis, Immunity,15(5), 837-46 (2001)
  6. Winkles J.A., The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting, Nat. Rev. Drug Discov.,7(5), 411-25 (2008)
  7. Culp P.A., Choi D., Zhang Y., Yin J., Seto P. and Ybarra S.E. et al., Antibodies to TWEAK receptor inhibits human tumor growth through dual mechanisms, Clin. Cancer Res.,16(2), 497-508 (2010)
  8. Han H., Bearss D.J., Browne L.W., Calaluce R., Nagle R.B. and Von Hoff D.D., Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarray, Cancer Res.,62(10), 2890-6 (2002)
  9. Wang S., Zhan M., Yin J., Abraham J.M., Mori Y. and Sato al. Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis, Oncogene, 25(23), 3346-56 (2006)
  10. Tran N.L., McDonough W.S., Savitch B.A., Fortin S.P., Winkles J.A. and Symons M. et al. Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor{kappa} B and correlate with poor patient outcome, Cancer Res.,66(19), 9535-42 (2006)
  11. Zhou H., John W., Walter N., YagitaH., Lawrence H. and Michael G. et al. Development and Characterization of a Potent Immunoconjugate Targeting the Fn14 Receptor on Solid Tumor Cells, Mol. Cancer Ther., 10(7), 1276–88(2011)
  12. Wang J., Liu Y., Wei M.J., Mi X.Y. and Wang E.H., Clinical correlations and prognostic relevance of Fn14 expression in breast carcinoma, Histol. Histopathol., 28(7), 859-64 (2013)
  13. Matos L.L., Stabenow E., Tavares M.R., Ferraz A.R., Capelozzi V.L. and Pinhal M.A., Immunohisto chemistry quantification by a digital computer-assisted method compared to semiquantitative analysis, Clinics., 61(5), 417-24 (2006)
  14. Ramos-Vara JA. and Miller M.A., When tissue antigens and antibodies get along: revisiting the technical aspects of immunohistochemistry—the red, brown, and blue technique, Vet Pathol.,51(1), 42-87 (2014)
  15. Chao D.T., Su M., Tanlimco S., Sho M., Choi D. andFox M. et al., Expression of TweakR in breast cancer and preclinical activity of enavatuzumab, a humanized anti-TweakRmAb, J Cancer Res Clin Oncol.,139(2), 315-25 (2013)
  16. Michaelson J.S., Amatucci A., Kelly R., Su L., Garber E., and Day E.S. et al., Development of an Fn14 agonistic antibody as an anti-tumor agent, MAbs., 3(4), 362-75 (2011)
  17. Kwon O.H., Kim J.H., Kim S.Y. and Kim Y.S., TWEAK/Fn14 signaling mediates gastric cancer cell resistance to 5-fluorouracil via NF-B activation, Int J Oncol.,44(2), 583-90 (2014)
  18. Gu L., Cao C., Zhu J., Ding C. and Xu H.B., Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention, P LoS One., 8(3), e57436 (2013)
  19. Asrani K., Keri R.A., Galisteo R., Brown S.A, Morgan S.J. and Ghosh A. et al., The HER2- and heregulin 1 (HRG)-inducible TNFR superfamily member Fn14 promotes HRG-driven breast cancer cell migration, invasion, and MMP9 expression, Mol Cancer Res.,11(4), 393-404 (2013)
  20. Willis A.L., Tran N.L., Chatigny J.M., Charlton N., Vu H. and Brown S.A. et al., The fibroblast growth factor-inducible 14 receptor is highly expressed in HER2-positive breast tumors and regulates breast cancer cell invasive capacity, Mol Cancer Res.,6(5), 725-34 (2008)
  21. Whitsett T.G., Mathews I.T., Cardone M.H., Lena R.J., Pierceall W.E. and Bittner M. et al. Mcl-1 mediates TWEAK/Fn14-induced non-small cell lung cancer survival and therapeutic response, Mol Cancer Res., 12(4), 550-9 (2014)
  22. Li N., Hu W.J., Shi J., Xue J., Guo W.X. and Zhang Y. et al., Roles of fibroblast growth factor-inducible 14 in hepatocellular carcinoma, Asian Pac J Cancer Prev.,14(6), 3509-14 (2013)
  23. Huang M., Narita S., Tsuchiya N., Ma Z., Numakura K. and Obara T. et al., Overexpression of Fn14 promotes androgen-independent prostate cancer progression through MMP-9 and correlates with poor treatment outcome, Carcinogenesis., 32(11), 1589-96 (2011)
  24. Als A.B., Dyrskjøt L., von der Maase H., Koed K., Mansilla F. and Toldbod H.E. et al., Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder, cancer. Clin Cancer Res.,13(15 Pt 1), 4407-14 (2007)
  25. Hsieh A.C. and Moasser M.M., Targeting HER proteins in cancer therapy and the role of the non-target HER3, Br J Cancer,97(4), 453-7 (2007)
  26. Biswas D.K. and Iglehart J.D., Linkage between EGFR family receptors and nuclear factor kappaB (NF-kappaB) signaling in breast cancer, J Cell Physiol.,209(3), 645-52(2006)