Is vimentin a potential prognostic factor for patients with triple-negative breast cancer?

Abstract

Objective

To evaluate the prognostic potential of vimentin, p53, EGFR, CK5/6, CK 14, and CK 17 in patients with triple-negative breast cancer (TNBC).

Material and methods

Tumor specimens of 60 patients with histologically confirmed TNBC were retrospectively analyzed. Formalin-fixed paraffin-embedded blocks of the tumor tissue were used to prepare tissue microarrays (TMAs). After immune-histochemical staining, protein expression of vimentin, p53, EGFR, CK5/6, CK 14, and CK 17 was determined and the immunoreactive score (IRS) was calculated. The protein expression was correlated to overall (OS) and disease-free survival (DFS).

Results

Ninety percent of patients suffered from an invasive ductal carcinoma T1 or T2, 66.7% were N0, and 70% had a G3 tumor with Ki67 of > 14%. Vimentin expression was found in 28/60 patients (46.7%), p53 expression in 30/60 patients (50%), and EGFR expression in 3/60 patients (5%). CK5/6, CK14, and CK17 expression was found in 60.0%, 63.3%, and 66.7%, respectively. Vimentin expression vs no expression was associated with significantly higher mean Ki67 values (52.5% vs. 31.1%; p = 0.0013) and significantly higher p53 expression (67.9% vs. 34.4%; p = 0.0097). No significant association between vimentin expression and OS (p = 0.7710) or DFS (p = 0.5558) was found during a mean follow-up of 92 months.

Conclusion

None of the six proteins proved to be suitable prognostic factors for OS and DSF in patients with TNBC.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3

References

  1. Adamo B, Ricciardi GRR, Ieni A, Franchina T, Fazzari C, Sano MV et al (2017) The prognostic significance of combined androgen receptor, E-Cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer. Oncotarget 8(44):76974–76986

    PubMed  PubMed Central  Article  Google Scholar 

  2. Arteaga CL, Engelman JA (2014) ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell 25(3):282–303

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. Bae SY, Nam SJ, Jung Y, Lee SB, Park BW, Lim W et al (2018) Differences in prognosis and efficacy of chemotherapy by p53 expression in triple-negative breast cancer. Breast Cancer Res Treat 172(2):437–444

    CAS  PubMed  Article  Google Scholar 

  4. Battaglia RA, Delic S, Herrmann H, Snider NT (2018) Vimentin on the move: new developments in cell migration. F1000Research:7

  5. Costa R, Shah AN, Santa-Maria CA, Cruz MR, Mahalingam D, Carneiro BA et al (2017) Targeting epidermal growth factor receptor in triple negative breast cancer: new discoveries and practical insights for drug development. Cancer Treat Rev 53:111–119

    CAS  PubMed  Article  Google Scholar 

  6. Dine JL, O'Sullivan CC, Voeller D, Greer YE, Chavez KJ, Conway CM et al (2016) The TRAIL receptor agonist drozitumab targets basal B triple-negative breast cancer cells that express vimentin and Axl. Breast Cancer Res Treat 155(2):235–251

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. D'Ippolito E, Iorio MV (2013) MicroRNAs and triple negative breast cancer. Int J Mol Sci 14(11):22202–22220

    PubMed  PubMed Central  Article  Google Scholar 

  8. Duffy MJ, Synnott NC, Crown J (2018) Mutant p53 in breast cancer: potential as a therapeutic target and biomarker. Breast Cancer Res Treat 170(2):213–219

    CAS  PubMed  Article  Google Scholar 

  9. El Hachem G, Gombos A, Awada A (2019) Recent advances in understanding breast cancer and emerging therapies with a focus on luminal and triple-negative breast cancer. F1000Research 8

  10. Hashmi AA, Naz S, Hashmi SK, Hussain ZF, Irfan M, Bakar SMA et al (2018) Cytokeratin 5/6 and cytokeratin 8/18 expression in triple negative breast cancers: clinicopathologic significance in South-Asian population. BMC Res Notes 11(1):372

    PubMed  PubMed Central  Article  Google Scholar 

  11. Heatley MK, Ewings P, Odling Smee W, Maxwell P, Toner PG (2002) Vimentin expression does not assist in predicting survival in ductal carcinoma of the breast. Pathology 34(3):230–232

    CAS  PubMed  Article  Google Scholar 

  12. Jeong H, Ryu YJ, An J, Lee Y, Kim A (2012) Epithelial-mesenchymal transition in breast cancer correlates with high histological grade and triple-negative phenotype. Histopathology 60(6B):E87–95

    PubMed  Article  Google Scholar 

  13. Jongen L, Floris G, Wildiers H, Claessens F, Richard F, Laenen A et al (2019) Tumor characteristics and outcome by androgen receptor expression in triple-negative breast cancer patients treated with neo-adjuvant chemotherapy. Breast Cancer Res Treat

  14. Kasoha M, Unger C, Solomayer EF, Bohle RM, Zaharia C, Khreich F et al (2017) Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases. Clin Exp Metastasis 34(8):479–490

    CAS  PubMed  Article  Google Scholar 

  15. Kim HS, Yom CK, Kim HJ, Lee JW, Sohn JH, Kim JH et al (2010) Overexpression of p53 is correlated with poor outcome in premenopausal women with breast cancer treated with tamoxifen after chemotherapy. Breast Cancer Res Treat 121(3):777–788

    CAS  PubMed  Article  Google Scholar 

  16. Korsching E, Packeisen J, Liedtke C, Hungermann D, Wulfing P, van Diest PJ et al (2005) The origin of vimentin expression in invasive breast cancer: epithelial-mesenchymal transition, myoepithelial histogenesis or histogenesis from progenitor cells with bilinear differentiation potential? J Pathol 206(4):451–457

    CAS  PubMed  Article  Google Scholar 

  17. Kusinska RU, Kordek R, Pluciennik E, Bednarek AK, Piekarski JH, Potemski P (2009) Does vimentin help to delineate the so-called 'basal type breast cancer'? J Exp Clin Cancer Res 28:118

    PubMed  PubMed Central  Article  Google Scholar 

  18. Li JP, Zhang XM, Zhang Z, Zheng LH, Jindal S, Liu YJ (2019a) Association of p53 expression with poor prognosis in patients with triple-negative breast invasive ductal carcinoma. Medicine (Baltimore) 98(18):e15449

    CAS  Article  Google Scholar 

  19. Li Y, Zhang X, Qiu J, Pang T, Huang L, Zeng Q (2019b) Comparisons of p53, KI67 and BRCA1 expressions in patients with different molecular subtypes of breast cancer and their relationships with pathology and prognosis. J BUON 24(6):2361–2368

    PubMed  Google Scholar 

  20. Lou L, Yu Z, Wang Y, Wang S, Zhao Y (2018) c-Src inhibitor selectively inhibits triple-negative breast cancer overexpressed Vimentin in vitro and in vivo. Cancer Sci 109(5):1648–1659

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I et al (2017) Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 376(22):2147–2159

    CAS  PubMed  Article  Google Scholar 

  22. Mathieu A, Weynand B, Verbeken E, Da Silva S, Decaestecker C, Salmon I et al (2010) Comparison of four antibodies for immunohistochemical evaluation of epidermal growth factor receptor expression in non-small cell lung cancer. Lung Cancer 69(1):46–50

    PubMed  Article  Google Scholar 

  23. Newman LA, Reis-Filho JS, Morrow M, Carey LA, King TA (2015) The 2014 society of surgical oncology Susan G. Komen for the cure symposium: triple-negative breast cancer. Ann Surg Oncol 22(3):874–82

  24. Plasilova ML, Hayse B, Killelea BK, Horowitz NR, Chagpar AB, Lannin DR (2016) Features of triple-negative breast cancer: Analysis of 38,813 cases from the national cancer database. Medicine (Baltimore) 95(35):e4614

    Article  Google Scholar 

  25. Rakha EA, El-Sayed ME, Green AR, Paish EC, Lee AH, Ellis IO (2007a) Breast carcinoma with basal differentiation: a proposal for pathology definition based on basal cytokeratin expression. Histopathology 50(4):434–438

    CAS  PubMed  Article  Google Scholar 

  26. Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO (2007b) Prognostic markers in triple-negative breast cancer. Cancer 109(1):25–32

    CAS  PubMed  Article  Google Scholar 

  27. Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Der Pathologe 8(3):138–140

    CAS  PubMed  Google Scholar 

  28. Sable M, Pai TD, Shet T, Patil A, Dhanavade S, Desai SB (2017) Triple-negative breast cancer: a comprehensive study of clinical, histomorphological, and immunohistochemical features in indian patients. Int J Surg Pathol 25(3):230–237

    PubMed  Article  Google Scholar 

  29. Schmidt G, Meyberg-Solomayer G, Gerlinger C, Juhasz-Boss I, Herr D, Rody A et al (2014) Identification of prognostic different subgroups in triple negative breast cancer by Her2-neu protein expression. Arch Gynecol Obstet 290(6):1221–1229

    CAS  PubMed  Article  Google Scholar 

  30. Schmidt G, Gerlinger C, Juhasz-Boss I, Stickeler E, Rody A, Liedtke C et al (2016) Her2-neu score as a prognostic factor for outcome in patients with triple-negative breast cancer. J Cancer Res Clin Oncol 142(6):1369–1376

    CAS  PubMed  Article  Google Scholar 

  31. Yamashita N, Tokunaga E, Kitao H, Hisamatsu Y, Taketani K, Akiyoshi S et al (2013) Vimentin as a poor prognostic factor for triple-negative breast cancer. J Cancer Res Clin Oncol 139(5):739–746

    CAS  PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Gilda Schmidt.

Ethics declarations

Conflict of interest

None of the authors declared any conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Schmidt, G., Solomayer, E., Bohle, R.M. et al. Is vimentin a potential prognostic factor for patients with triple-negative breast cancer?. J Cancer Res Clin Oncol 146, 2109–2116 (2020). https://doi.org/10.1007/s00432-020-03210-0

Download citation

Keywords

  • Triple-negative breast cancer
  • Vimentin
  • p53
  • EGFR
  • Cytokines