Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 5/2013

01-05-2013 | Original Paper

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

Authors: Nami Yamashita, Eriko Tokunaga, Hiroyuki Kitao, Yuichi Hisamatsu, Kenji Taketani, Sayuri Akiyoshi, Satoko Okada, Shinichi Aishima, Masaru Morita, Yoshihiko Maehara

Published in: Journal of Cancer Research and Clinical Oncology | Issue 5/2013

Login to get access

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.
Literature
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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):1059–1064PubMed 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):1059–1064PubMed
go back to reference 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):2795–2807PubMedCrossRef 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):2795–2807PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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):679–691PubMedCrossRef 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):679–691PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
go back to reference 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):5168–5178PubMed 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):5168–5178PubMed
Metadata
Title
Vimentin as a poor prognostic factor for triple-negative breast cancer
Authors
Nami Yamashita
Eriko Tokunaga
Hiroyuki Kitao
Yuichi Hisamatsu
Kenji Taketani
Sayuri Akiyoshi
Satoko Okada
Shinichi Aishima
Masaru Morita
Yoshihiko Maehara
Publication date
01-05-2013
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 5/2013
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-013-1376-6

Other articles of this Issue 5/2013

Journal of Cancer Research and Clinical Oncology 5/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.