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High preoperative serum TIMP-1 is a prognostic indicator for survival in breast carcinoma

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Abstract

The amount of the immunoreactive protein for the tissue inhibitor of the matrix metalloproteinase-1 (TIMP-1) was studied prospectively from the pretreatment sera of 71 breast carcinoma patients using an enzyme-linked immunoassay (ELISA). The study consisted of patients with a primary breast carcinoma diagnosed between 1988 and 1991. The median follow-up time was more than 10 years, and routine adjuvant treatment was not used in the primary treatment. High TIMP-1 (> 196 ng/ml) was found to correlate with a poor relapse-free survival (RFS) in primary node-negative breast carcinoma. After 10 years of the follow-up only 42% of the patients with a high preoperative serum TIMP-1-level were free of the relapse, whereas 82% of the patients with a low serum TIMP-1 enjoyed a long RFS-time (log rank p =0.009). High serum TIMP-1 also indicated poor RFS (p=0.02) and overall survival (p=0.05) in stage I breast carcinoma. In Kaplan–Meier analysis the RFS was 89% in patients with a low serum level of TIMP-1 compared to 52% in patients with a high serum concentration of TIMP-1. In conclusion, preoperative high serum TIMP-1 levels predict poor outcome in primary breast carcinoma. In multivariate analysis preoperative high serum TIMP-1 increases the risk of relapse 3.4-fold during the first 10 years of follow-up in primary node-negative breast carcinoma.

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References

  • LA Liotta PS Steeg WG Stetler-Stevenson (1991) ArticleTitleCancer metastasis and angiogenesis: an imbalance of positive and negative regulation Cell 64 327–336 Occurrence Handle10.1016/0092-8674(91)90642-C Occurrence Handle1:CAS:528:DyaK3MXpvFWktA%3D%3D Occurrence Handle1703045

    Article  CAS  PubMed  Google Scholar 

  • DT Denhardt B Feng DR Edwards ET Cocuzzi UM Malyankar (1993) ArticleTitleTissue inhibitor of metalloproteinases (TIMP, aka EPA): structure, control of expression and biological functions Pharmacol Ther 59 329–341 Occurrence Handle8309995 Occurrence Handle1:CAS:528:DyaK2cXltVOjsw%3D%3D

    PubMed  CAS  Google Scholar 

  • LA Liotta WG Stetler-Stevenson (1990) ArticleTitleMetalloproteinases and cancer invasion Semin Cancer Biol 1 99–106 Occurrence Handle2103492 Occurrence Handle1:STN:280:DyaK3MzlsF2lsw%3D%3D

    PubMed  CAS  Google Scholar 

  • H Iwata S Kobayashi H Iwase A Masaoka N Fujimoto Y Okada (1996) ArticleTitleProduction of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human breast carcinomas Jpn J Cancer Res 87 602–611 Occurrence Handle8766524 Occurrence Handle1:CAS:528:DyaK28XjvVOit7c%3D

    PubMed  CAS  Google Scholar 

  • EA Garbett MW Reed NJ Brown (1999) ArticleTitleProteolysis in breast and colorectal cancer Br J Cancer 8 287–293

    Google Scholar 

  • EA Garbett MW Reed TJ Stephenson NJ Brown (2000) ArticleTitleProteolysis in human breast cancer J Clin Pathol 53 99–106 Occurrence Handle10.1136/mp.53.2.99 Occurrence Handle1:CAS:528:DC%2BD3cXivFOnurc%3D

    Article  CAS  Google Scholar 

  • BEA Stephenson TJ Reed NJ Brown (2002) ArticleTitleExpression of proteinases and inhibitors in human breast cancer progression and survival Mol Pathol 55 300–304 Occurrence Handle12354933

    PubMed  Google Scholar 

  • A Talvensaari-Mattila P Pääkkö M Höyhtyä G Blanco-Sequeiros T Turpeenniemi-Hujanen (1998) ArticleTitleMatrix metalloproteinase-2 immunoreactive protein, a marker of aggressiveness in breast carcinoma Cancer 83 1153–1162 Occurrence Handle9740080 Occurrence Handle1:CAS:528:DyaK1cXmtlegsrg%3D

    PubMed  CAS  Google Scholar 

  • R Hirvonen A Talvensaari-Mattila P Pääkkö T Turpeenniemi-Hujanen (2003) ArticleTitleMatrix metalloproteinase-2 (MMP-2) in T1-2N0 breast carcinoma Breast Cancer Res Treat 77 85–91 Occurrence Handle12602907 Occurrence Handle1:CAS:528:DC%2BD38XovVCltLk%3D

    PubMed  CAS  Google Scholar 

  • A Talvensaari-Mattila P Pääkkö T Turpeenniemi-Hujanen (2003) ArticleTitleMatrix metalloproteinase-2 (MMP-2) is associated with survival in breast carcinoma Br J Cancer 89 1270–1275 Occurrence Handle14520459 Occurrence Handle1:CAS:528:DC%2BD3sXns1Cmur0%3D

    PubMed  CAS  Google Scholar 

  • L Nakopoulou I Giannopoulou K Stefanaki E Panayotopoulou I Tsirmpa P Alexandrou J Mavrommatis S Katsarou P Davaris (2002) ArticleTitleEnhanced mRNA expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in breast carcinomas is correlated with adverse prognosis J Pathol 197 307–313 Occurrence Handle12115876 Occurrence Handle1:CAS:528:DC%2BD38XmtVSkur0%3D

    PubMed  CAS  Google Scholar 

  • L Nakopoulou I Giannopoulou ACh Lazaris P Alexandrou I Tsirmpa S Markaki E Panayotopoulou A Keramopoulos (2003) ArticleTitleThe favorable prognostic impact of tissue inhibitor of matrix metalloproteinases-1 protein overexpression in breast cancer cells APMIS 111 1023–1036

    Google Scholar 

  • A Väisänen M Kallioinen PJ Taskinen T Turpeenniemi-Hujanen (1998) ArticleTitlePrognostic value of MMP-2 immunoreactive protein (72 kD type IV collagenase) in primary skin melanoma J Pathol 186 51–58 Occurrence Handle9875140

    PubMed  Google Scholar 

  • A Väisänen M Kallioinen K von Dickhoff L Laatikainen M Höyhtyä T Turpeenniemi-Hujanen (1999) ArticleTitleMatrix metalloproteinase-2 (MMP-2) immunoreactive protein A new prognostic marker in uveal melanoma? J Pathol 188 56–62

    Google Scholar 

  • B Davidson I Goldberg WH Gotlieb J Kopolovic G Ben-Baruch JM Nesland A Berner M Bryne R Reich (1999) ArticleTitleHigh levels of MMP-2, MMP-9, MT1-MMP and TIMP-2 mRNA correlate with poor survival in ovarian carcinoma Clin Exp Metastasis 17 799–808 Occurrence Handle11089877 Occurrence Handle1:CAS:528:DC%2BD3cXos1Oku7s%3D

    PubMed  CAS  Google Scholar 

  • S Ylisirniö M Höyhtyä T Turpeenniemi-Hujanen (2000) ArticleTitleSerum matrix metalloproteinase-2, -9 and tissue inhibitors of metalloproteinase-1, -2 in lung cancer–TIMP-1 as a prognostic marker Anticancer Res 20 1311–1316 Occurrence Handle10810441

    PubMed  Google Scholar 

  • S Ylisirniö M Höyhtyä R Mäkitaro P Pääkkö J Risteli VL Kinnula T Turpeenniemi-Hujanen A Jukkola (2001) ArticleTitleElevated serum levels of type I collagen degradation marker ICTP and tissue inhibitor of metalloproteinase (TIMP) 1 are associated with poor prognosis in lung cancer Clin Cancer Res 7 1633–1637 Occurrence Handle11410500

    PubMed  Google Scholar 

  • MN Holten-Andersen G Murphy HJ Nielsen AN Pedersen IJ Christe G Hoyer-Hansen N Brunner RW Stephens (1999) ArticleTitleQuantitation of TIMP-1 in plasma of healthy blood donors and patients with advanced cancer. Br J Cancer 80 IssueID(3–4) 495–503 Occurrence Handle10408859 Occurrence Handle1:STN:280:DyaK1MzhsVOkug%3D%3D

    PubMed  CAS  Google Scholar 

  • MN Holten-Andersen RW Stephens HJ Nielsen G Murphy IJ Christensen W Stetler-Stevenson N Brunner (2000) ArticleTitleHigh preoperative plasma tissue inhibitor of metalloproteinase-1 levels are associated with short survival of patients with colorectal cancer Clin Cancer Res 6 4292–4299 Occurrence Handle11106246 Occurrence Handle1:CAS:528:DC%2BD3cXovVSgur0%3D

    PubMed  CAS  Google Scholar 

  • RW Scarff H Torloni (1986) Histological Typing of Breast Tumours. WHO Geneva

    Google Scholar 

  • EL Kaplan P Meier (1958) ArticleTitleNonparametric estimation from incomplete observations J Am Stat Assoc 53 457–481

    Google Scholar 

  • N Mantel (1966) ArticleTitleEvaluation of survival data and two new rank order statistics arising in this consideration Cancer Chemother Rep 50 163–170 Occurrence Handle1:STN:280:DyaF287ht1Wgug%3D%3D Occurrence Handle5910392

    CAS  PubMed  Google Scholar 

  • N Yukawa T Yoshikawa M Akaike Y Sugimasa S Takemiya S Yanoma Y Noguchi Y Takanashi (2001) ArticleTitlePlasma concentration of tissue inhibitor of matrix metalloproteinase 1 in patients with colorectal carcinoma Br J Surg 88 1596–1601 Occurrence Handle11736971 Occurrence Handle1:STN:280:DC%2BD3MnptVGmsg%3D%3D

    PubMed  CAS  Google Scholar 

  • K McCarthy T Maguire G McGreal E McDermott N O’Higgins MJ Duffy (1999) ArticleTitleHigh levels of tissue inhibitor of metalloproteinase-1 predict poor outcome in patients with breast carcinoma Int J Cancer 84 44–48 Occurrence Handle9988231 Occurrence Handle1:STN:280:DyaK1M7ktVOgsg%3D%3D

    PubMed  CAS  Google Scholar 

  • MN Holten-Andersen IJ Christensen HJ Nielsen RW Stephens V Jensen OH Nielsen S Sörensen J Overgaard H Lilja A Harris G Murphy N Brunner (2002) ArticleTitleTotal levels of tissue inhibitor of metalloproteinases 1 in plasma yield high diagnostic sensitivity and specificity in patients with colon cancer Clin Cancer Res 8 156–164 Occurrence Handle11801553 Occurrence Handle1:CAS:528:DC%2BD38XhsVKmurg%3D

    PubMed  CAS  Google Scholar 

  • A Remacle K McCarthy A Noel T Maguire E McDermott N O’Higgis JM Foidart MJ Duffy (2000) ArticleTitleHigh levels of TIMP-2 correlate with adverse prognosis in breast cancer. Int J Cancer 20 89 IssueID2 118–121 Occurrence Handle1:CAS:528:DC%2BD3cXislehsr0%3D

    CAS  Google Scholar 

  • T Yoshikawa A Tsuburaya O Kobayashi M Sairenji H Motohashi S Yanoma Y Noguchi (2000) ArticleTitlePrognostic value of tissue inhibitor of matrix metalloproteinase-1 in plasma of patients with gastric cancer Cancer Lett. 151 IssueID1 81–86 Occurrence Handle10766426 Occurrence Handle1:CAS:528:DC%2BD3cXitFKrt7c%3D

    PubMed  CAS  Google Scholar 

  • H Susskind MH Hymowitz YH Lau HL Atkins AN Hurewitz ES Valentine AG Meek S Zucker (2003) ArticleTitleIncreased plasma levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in lung and breast cancer are altered during chest radiotherapy. Int J Radiat Oncol Biol Phys 56 IssueID4 1161–1169 Occurrence Handle12829155 Occurrence Handle1:CAS:528:DC%2BD3sXkvVClu7s%3D

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Oulu University Hospital, Box 24, FIN 90029 OYS

    Anne Talvensaari-Mattila

  2. Department of Oncology and Radiotherapy, University of Oulu and University Hospital of Oulu, Finland

    Taina Turpeenniemi-Hujanen

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  1. Anne Talvensaari-Mattila
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  2. Taina Turpeenniemi-Hujanen
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Correspondence to Anne Talvensaari-Mattila.

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Talvensaari-Mattila, A., Turpeenniemi-Hujanen, T. High preoperative serum TIMP-1 is a prognostic indicator for survival in breast carcinoma. Breast Cancer Res Treat 89, 29–34 (2005). https://doi.org/10.1007/s10549-004-1006-8

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  • DOI: https://doi.org/10.1007/s10549-004-1006-8

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