Skip to main content

Advertisement

Log in

Vimentin as a poor prognostic factor for triple-negative breast cancer

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, is a highly heterogeneous disease. Recent studies suggest that there are links between TNBC and the epithelial-mesenchymal transition (EMT). To identify prognostic biomarkers and novel therapeutic targets, vimentin, one of the most major factors associated with EMT was investigated in TNBC.

Materials and methods

Sporadic invasive ductal carcinoma specimens were obtained from 659 Japanese patients, and 90 (14 %) cases were diagnosed as TNBC. The vimentin mRNA and protein expression levels were evaluated by quantitative reverse transcriptase–polymerase chain reaction and immunohistochemistry.

Results

The mRNA expression of vimentin was significantly upregulated in the basal-type breast cancer cell line. Immunohistochemically, the vimentin expression was significantly higher (p = 0.0042) in TNBC compared with the other subtypes. Vimentin expression was associated with a younger age (p = 0.016), high nuclear grade (p = 0.023) and high Ki67 expression (p < 0.0001), and a poorer prognosis in terms of both the recurrence-free survival (RFS) (p = 0.0058) and overall survival (OS) (p = 0.013) in TNBC patients. A multivariate analysis showed that vimentin expression was an independent prognostic factor for the RFS (p = 0.043). Vimentin expression was also associated with a significantly shorter RFS (p = 0.021) and OS (p = 0.017) in patients with basal-like breast cancer (BLBC).

Conclusions

The elevated expression of vimentin contributes to the aggressive phenotype and poor prognosis in TNBC. Vimentin expression might be useful as a biomarker for the prognosis of TNBC.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aroeira LS, Aguilera A, Sanchez-Tomero JA, Bajo MA, del Peso G, Jimenez-Heffernan JA, Selgas R, Lopez-Cabrera M (2007) Epithelial to mesenchymal transition and peritoneal membrane failure in peritoneal dialysis patients: pathologic significance and potential therapeutic interventions. J Am Soc Nephrol 18(7):2004–2013. doi:10.1681/ASN.2006111292

    Article  PubMed  CAS  Google Scholar 

  • Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13(8):2329–2334. doi:10.1158/1078-0432.CCR-06-1109

    Article  PubMed  CAS  Google Scholar 

  • Cleator S, Heller W, Coombes RC (2007) Triple-negative breast cancer: therapeutic options. Lancet Oncol 8(3):235–244. doi:10.1016/S1470-2045(07)70074-8

    Article  PubMed  Google Scholar 

  • Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13(15 Pt 1):4429–4434. doi:10.1158/1078-0432.CCR-06-3045

    Article  PubMed  Google Scholar 

  • Dent R, Hanna WM, Trudeau M, Rawlinson E, Sun P, Narod SA (2009) Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res Treat 115(2):423–428. doi:10.1007/s10549-008-0086-2

    Article  PubMed  Google Scholar 

  • Domagala W, Wozniak L, Lasota J, Weber K, Osborn M (1990) Vimentin is preferentially expressed in high-grade ductal and medullary, but not in lobular breast carcinomas. Am J Pathol 137(5):1059–1064

    PubMed  CAS  Google Scholar 

  • Dudley AT, Lyons KM, Robertson EJ (1995) A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev 9(22):2795–2807

    Article  PubMed  CAS  Google Scholar 

  • Gjerdrum C, Tiron C, Hoiby T, Stefansson I, Haugen H, Sandal T, Collett K, Li S, McCormack E, Gjertsen BT, Micklem DR, Akslen LA, Glackin C, Lorens JB (2010) Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival. Proc Natl Acad Sci USA 107(3):1124–1129. doi:10.1073/pnas.0909333107

    Article  PubMed  CAS  Google Scholar 

  • Green KJ, Bohringer M, Gocken T, Jones JC (2005) Intermediate filament associated proteins. Adv Protein Chem 70:143–202. doi:10.1016/S0065-3233(05)70006-1

    Article  PubMed  CAS  Google Scholar 

  • Gupta GP, Massague J (2006) Cancer metastasis: building a framework. Cell 127(4):679–695. doi:10.1016/j.cell.2006.11.001

    Article  PubMed  CAS  Google Scholar 

  • Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, Harris L, Hait W, Toppmeyer D (2006) Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol 24(36):5652–5657. doi:10.1200/JCO.2006.06.5664

    Article  PubMed  Google Scholar 

  • 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. doi:10.1080/00313020220131273

    Article  PubMed  CAS  Google Scholar 

  • Holland SJ, Powell MJ, Franci C, Chan EW, Friera AM, Atchison RE, McLaughlin J, Swift SE, Pali ES, Yam G, Wong S, Lasaga J, Shen MR, Yu S, Xu W, Hitoshi Y, Bogenberger J, Nor JE, Payan DG, Lorens JB (2005) Multiple roles for the receptor tyrosine kinase axl in tumor formation. Cancer Res 65(20):9294–9303. doi:10.1158/0008-5472.CAN-05-0993

    Article  PubMed  CAS  Google Scholar 

  • Jatoi I, Anderson WF, Jeong JH, Redmond CK (2011) Breast cancer adjuvant therapy: time to consider its time-dependent effects. J Clin Oncol 29(17):2301–2304. doi:10.1200/JCO.2010.32.3550

    Article  PubMed  Google Scholar 

  • 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–E95. doi:10.1111/j.1365-2559.2012.04195.x

    Article  PubMed  Google Scholar 

  • Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier J, Housman D, Jaenisch R (1993) WT-1 is required for early kidney development. Cell 74(4):679–691

    Article  PubMed  CAS  Google Scholar 

  • 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. doi:10.1186/1756-9966-28-118

    Article  PubMed  Google Scholar 

  • Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121(7):2750–2767. doi:10.1172/JCI45014

    Article  PubMed  CAS  Google Scholar 

  • Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, Cristofanilli M, Hortobagyi GN, Pusztai L (2008) Response to neo adjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26(8):1275–1281. doi:10.1200/JCO.2007.14.4147

    Article  PubMed  Google Scholar 

  • Metzger-Filho O, Tutt A, de Azambuja E, Saini KS, Viale G, Loi S, Bradbury I, Bliss JM, Azim HA Jr, Ellis P, Di Leo A, Baselga J, Sotiriou C, Piccart-Gebhart M (2012) Dissecting the heterogeneity of triple-negative breast cancer. J Clin Oncol 30(15):1879–1887. doi:10.1200/JCO.2011.38.2010

    Article  PubMed  CAS  Google Scholar 

  • Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, Akslen LA, Ragaz J, Gown AM, Gilks CB, van de Rijn M, Perou CM (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10(16):5367–5374. doi:10.1158/1078-0432.CCR-04-0220

    Article  PubMed  CAS  Google Scholar 

  • Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752. doi:10.1038/35021093

    Article  PubMed  CAS  Google Scholar 

  • Sarrio D, Rodriguez-Pinilla SM, Hardisson D, Cano A, Moreno-Bueno G, Palacios J (2008) Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res 68(4):989–997. doi:10.1158/0008-5472.CAN-07-2017

    Article  PubMed  CAS  Google Scholar 

  • Satelli A, Li S (2011) Vimentin in cancer and its potential as a molecular target for cancer therapy. Cell Mol Life Sci 68(18):3033–3046. doi:10.1007/s00018-011-0735-1

    Article  PubMed  CAS  Google Scholar 

  • Savagner P (2001) Leaving the neighborhood: molecular mechanisms involved during epithelial-mesenchymal transition. BioEssays 23(10):912–923. doi:10.1002/bies.1132

    Article  PubMed  CAS  Google Scholar 

  • Seshadri R, Raymond WA, Leong AS, Horsfall DJ, McCaul K (1996) Vimentin expression is not associated with poor prognosis in breast cancer. Int J Cancer 67(3):353–356. doi:10.1002/(SICI)1097-0215(19960729)67:3<353:AID-IJC8>3.0.CO;2-Q

    Article  PubMed  CAS  Google Scholar 

  • Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, Brown PO, Borresen-Dale AL, Botstein D (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100(14):8418–8423. doi:10.1073/pnas.0932692100

    Article  PubMed  CAS  Google Scholar 

  • Stark K, Vainio S, Vassileva G, McMahon AP (1994) Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 372(6507):679–683. doi:10.1038/372679a0

    Article  PubMed  CAS  Google Scholar 

  • Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2(6):442–454. doi:10.1038/nrc822

    Article  PubMed  CAS  Google Scholar 

  • Thompson EW, Paik S, Brunner N, Sommers CL, Zugmaier G, Clarke R, Shima TB, Torri J, Donahue S, Lippman ME et al (1992) Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines. J Cell Physiol 150(3):534–544. doi:10.1002/jcp.1041500314

    Article  PubMed  CAS  Google Scholar 

  • Thompson EW, Newgreen DF, Tarin D (2005) Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition? Cancer Res 65(14):5991–5995. doi:10.1158/0008-5472.CAN-05-0616 discussion 5995

    Article  PubMed  CAS  Google Scholar 

  • Tokunaga E, Kimura Y, Oki E, Ueda N, Futatsugi M, Mashino K, Yamamoto M, Ikebe M, Kakeji Y, Baba H, Maehara Y (2006) Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone-treated patients. Int J Cancer 118(2):284–289. doi:10.1002/ijc.21358

    Article  PubMed  CAS  Google Scholar 

  • Zajchowski DA, Bartholdi MF, Gong Y, Webster L, Liu HL, Munishkin A, Beauheim C, Harvey S, Ethier SP, Johnson PH (2001) Identification of gene expression profiles that predict the aggressive behavior of breast cancer cells. Cancer Res 61(13):5168–5178

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Mrs. Naoko Katakura, Mrs. Mariko Shimokawa, and Ms. Yuko Kubota for their valuable technical assistance and Mrs. Satoko Hamatake for her excellent secretarial assistance.

Conflict of interest

The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eriko Tokunaga.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamashita, N., Tokunaga, E., Kitao, H. et al. Vimentin as a poor prognostic factor for triple-negative breast cancer. J Cancer Res Clin Oncol 139, 739–746 (2013). https://doi.org/10.1007/s00432-013-1376-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-013-1376-6

Keywords

Navigation