Skip to main content

Advertisement

SpringerLink
Log in

KPNA2 protein expression in invasive breast carcinoma and matched peritumoral ductal carcinoma in situ

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The aim of this study was to evaluate protein expression of Karyopherin alpha 2 (KPNA2) in invasive breast cancer and matched ductal carcinoma in situ (DCIS) and to correlate it with clinicopathological data, including patient survival. KPNA2 protein expression was assessed by immunohistochemistry in breast tissue samples, containing invasive carcinomas, DCIS, and adjacent histologically benign breast tissues. A polyclonal goat KPNA2 antibody was used for immunostaining of 83 clinicopathologically characterized cases. For statistical analysis, staining of at least 10% of nuclei was considered KPNA2 positive. Immunohistochemical detection of KPNA2 in invasive carcinoma showed a significant correlation with higher tumor stage, positive lymph node status, higher tumor grade, and negative ER status. Concordantly, KPNA2-positive tumors (31.3%) showed significantly shorter disease-free survival times (69 months vs 118 months; p = 0.007). KPNA2 protein expression was also detected in DCIS (21.3%) adjacent to invasive tumor and correlated with nuclear grade (p = 0.013). Expression of KPNA2 in invasive breast cancer correlates with conventional prognostic parameters and shorter disease-free survival. Additionally, KPNA2 is overexpressed in DCIS, particularly high grade lesions, which emphasizes its potential role in carcinogenesis of invasive breast carcinomas.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Chook YM, Blobel G (2001) Karyopherins and nuclear import. Curr Opin Struct Biol 11(6):703–715

    Article  PubMed  CAS  Google Scholar 

  2. Dahl E, Kristiansen G, Gottlob K, Klaman I, Ebner E, Hinzmann B, Hermann K, Pilarsky C, Durst M, Klinkhammer-Schalke M, Blaszyk H, Knuechel R, Hartmann A, Rosenthal A, Wild PJ (2006) Molecular profiling of laser-microdissected matched tumor and normal breast tissue identifies karyopherin alpha2 as a potential novel prognostic marker in breast cancer. Clin Cancer Res 12(13):3950–3960

    Article  PubMed  CAS  Google Scholar 

  3. Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19:403–410

    Article  PubMed  CAS  Google Scholar 

  4. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57(1):43–66

    Article  PubMed  Google Scholar 

  5. Kim IS, Kim DH, Han SM, Chin MU, Nam HJ, Cho HP, Choi SY, Song BJ, Kim ER, Bae YS, Moon YH (2000) Truncated form of importin alpha identified in breast cancer cell inhibits nuclear import of p53. J Biol Chem 275(30):23139–23145

    Article  PubMed  CAS  Google Scholar 

  6. Klein A, Wessel R, Graessmann M, Jürgens M, Petersen I, Schmutzler R, Niederacher D, Arnold N, Meindl A, Scherneck S, Seitz S, Graessmann A (2007) Comparison of gene expression data from human and mouse breast cancers: identification of a conserved breast tumor gene set. Int J Cancer 121(3):683–688

    Article  PubMed  CAS  Google Scholar 

  7. Klopocki E, Kristiansen G, Wild PJ, Klaman I, Castanos-Velez E, Singer G, Stohr R, Simon R, Sauter G, Leibiger H, Essers L, Weber B, Hermann K, Rosenthal A, Hartmann A, Dahl E (2004) Loss of SFRP1 is associated with breast cancer progression and poor prognosis in early stage tumors. Int J Oncol 25(3):641–649

    PubMed  CAS  Google Scholar 

  8. Kristiansen G, Winzer KJ, Mayordomo E, Bellach J, Schluns K, Denkert C, Dahl E, Pilarsky C, Altevogt P, Guski H, Dietel M (2003) CD24 expression is a new prognostic marker in breast cancer. Clin Cancer Res 9(13):4906–4913

    PubMed  CAS  Google Scholar 

  9. Manders P, Tjan-Heijnen VC, Span PN, Grebenchtchikov N, Geurts-Moespot A, van Tienoven DT, Beex LV, Sweep FC (2004) Complex of urokinase-type plasminogen activator with its type 1 inhibitor predicts poor outcome in 576 patients with lymph node-negative breast carcinoma. Cancer 101(3):486–494

    Article  PubMed  CAS  Google Scholar 

  10. Nakopoulou L, Giannopoulou I, Stefanaki K, Panayotopoulou E, Tsirmpa I, Alexandrou P, Mavrommatis J, Katsarou S, Davaris P (2002) Enhanced mRNA expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in breast carcinomas is correlated with adverse prognosis. J Pathol 197(3):307–313

    Article  PubMed  CAS  Google Scholar 

  11. Poon IK, Jans DA (2005) Regulation of nuclear transport: central role in development and transformation? Traffic 6(3):173–186

    Article  PubMed  CAS  Google Scholar 

  12. Rudland PS, Platt-Higgins A, El-Tanani M, De Silva Rudland S, Barraclough R, Winstanley JH, Howitt R, West CR (2002) Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res 62(12):3417–3427

    PubMed  CAS  Google Scholar 

  13. Ryan BM, Konecny GE, Kahlert S, Wang HJ, Untch M, Meng G, Pegram MD, Podratz KC, Crown J, Slamon DJ, Duffy MJ (2006) Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1. Ann Oncol 17(4):597–604

    Article  PubMed  CAS  Google Scholar 

  14. Sobin LH, Fleming ID (1997) TNM Classification of Malignant Tumors, fifth edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer 80:1803–1804

    Article  PubMed  CAS  Google Scholar 

  15. Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, Nordgren H, Farmer P, Praz V, Haibe-Kains B, Desmedt C, Larsimont D, Cardoso F, Peterse H, Nuyten D, Buyse M, Van de Vijver MJ, Bergh J, Piccart M, Delorenzi M (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 98(4):262–272

    Article  PubMed  CAS  Google Scholar 

  16. Span PN, Tjan-Heijnen VC, Manders P, van Tienoven D, Lehr J, Sweep FC (2006) High survivin predicts a poor response to endocrine therapy, but a good response to chemotherapy in advanced breast cancer. Breast Cancer Res Treat 98(2):223–230

    Article  PubMed  CAS  Google Scholar 

  17. Spizzo G, Went P, Dirnhofer S, Obrist P, Simon R, Spichtin H, Maurer R, Metzger U, von Castelberg B, Bart R, Stopatschinskaya S, Kochli OR, Haas P, Mross F, Zuber M, Dietrich H, Bischoff S, Mirlacher M, Sauter G, Gastl G (2004) High Ep-CAM expression is associated with poor prognosis in node-positive breast cancer. Breast Cancer Res Treat 86(3):207–213

    Article  PubMed  CAS  Google Scholar 

  18. Thakur S, Zhang HB, Peng Y, Le H, Carroll B, Ward T, Yao J, Farid LM, Couch FJ, Wilson RB, Weber BL (1997) Localization of BRCA1 and a splice variant identifies the nuclear localization signal. Mol Cell Biol 17(1):444–452

    PubMed  CAS  Google Scholar 

  19. Wang Y, Klijn JG, Zhang Y, Sieuwerts AM, Look MP, Yang F, Talantov D, Timmermans M, Meijer-van Gelder ME, Yu J, Jatkoe T, Berns EM, Atkins D, Foekens JA (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365(9460):671–679

    PubMed  CAS  Google Scholar 

  20. Yousef GM, Scorilas A, Kyriakopoulou LG, Rendl L, Diamandis M, Ponzone R, Biglia N, Giai M, Roagna R, Sismondi P, Diamandis EP (2002) Human kallikrein gene 5 (KLK5) expression by quantitative PCR: an independent indicator of poor prognosis in breast cancer. Clin Chem 48(8):1241–1250

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pathology, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Charitéplatz 1, 10098, Berlin, Germany

    Anja Dankof, Florian R. Fritzsche, Stefan Pahl & Manfred Dietel

  2. Institute of Pathology, RWTH Aachen, Aachen, Germany

    Edgar Dahl

  3. Breast Centre, Charité, Universitätsmedizin Berlin, Berlin, Germany

    Glen Kristiansen

  4. Institute of Clinical Pathology, University Hospital Zürich, Zürich, Switzerland

    Peter Wild

  5. Department of Pathology, University Erlangen, Krankenhausstr 12, 91054, Erlangen, Germany

    Arndt Hartmann

  6. Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Germany

    Glen Kristiansen

Authors
  1. Anja Dankof
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Florian R. Fritzsche
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Edgar Dahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stefan Pahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter Wild
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Manfred Dietel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Arndt Hartmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Glen Kristiansen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Glen Kristiansen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dankof, A., Fritzsche, F.R., Dahl, E. et al. KPNA2 protein expression in invasive breast carcinoma and matched peritumoral ductal carcinoma in situ. Virchows Arch 451, 877–881 (2007). https://doi.org/10.1007/s00428-007-0513-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-007-0513-5

Keywords

Search

Navigation