Breast Cancer Research and Treatment

, Volume 65, Issue 1, pp 55–61 | Cite as

Matrix Metalloproteinase-2 (MMP-2) is Associated with the Risk for a Relapse in Postmenopausal Patients with Node-Positive Breast Carcinoma Treated with Antiestrogen Adjuvant Therapy

  • A. Talvensaari-Mattila
  • P. Pääkkö
  • G. Blanco-Sequeiros
  • T. Turpeenniemi-Hujanen
Conference Report

Abstract

Node-positive breast carcinoma is an aggressive disease. Postmenopausal patients benefit from antiestrogen adjuvant therapy. Predictive markers could, however, be useful in selecting these patients for different modalities of adjuvant therapy. Recently, we showed that MMP-2 (72kD type IV collagenase/gelatinase A) is correlated with unfavorable prognosis in premenopausal breast carcinoma patients. Expression of the immunoreactive protein for MMP-2 was evaluated prospectively in this study in paraffin tissue sections from primary tumors of 100 postmenopausal, node-positive breast carcinoma patients treated with an adjuvant antiestrogen therapy. A specific MMP-2 monoclonal antibody in an avidin–biotin immunohistochemical staining was used. Sixty nine percent of the samples were MMP-2 positive. Eighty three percent of the MMP-2 negative patients lived for 5 years without a recurrence, while only 67% of the patients with an MMP-2 positive primary tumor were recurrence-free at that time (p<0.0; log rank analysis). MMP-2 positivity showed a significant correlation with shortened survival in patients with a small primary tumor (T1–2) and a low axillary tumor burden. One hundred percent of these patients with an MMP-2 negative breast carcinoma survived for 5 years, compared to 73% of the MMP-2 positive cases alive at that time (p=0.02). In conclusion, we show here that MMP-2 is a prognostic indicator in postmenopausal patients with node-positive breast carcinoma with a low tumor burden, and that it predicts a risk for failure in antiestrogen adjuvant therapy. It might have predictive value in selecting the most efficient adjuvant therapy in this set of patients.

breast cancer gelatinase A prognosis prognostic factor survival type IV collagenase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ries LG, Pollack ES, Young JL: Cancer patients survival: surveillance, epidemiology, and end results. J Natl Cancer Inst 70: 693-707, 1983Google Scholar
  2. 2.
    Shetty MR, Reiman HM Jr: Tumor size and axillary metastasis, a correlative occurence in 1244 cases of breast cancer between 1980 and 1995. Eur J Surg Oncol 23(2): 139-141, 1997Google Scholar
  3. 3.
    Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S: Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 284: 67-68, 1980Google Scholar
  4. 4.
    Turpeenniemi-Hujanen T, Thorgeirsson UP, Hart IR, Grant SS, Liotta LA: Expression of collagenase IV (basement membrane collagenase) activity in murine tumor cell hybrids which differ in metastatic potential. J Natl Cancer Inst 75: 99-103, 1985Google Scholar
  5. 5.
    Nakajima M, Welch DR, Belloni PN, Nicolson GL: Degradation of basement membrane type IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell clones of differing metastatic potentials. Cancer Res 47: 4869-4876, 1987Google Scholar
  6. 6.
    Väisänen A, Kallioinen M, Taskinen PJ, Turpeenniemi-Hujanen T: Prognostic value of MMP-2 immunoreactive protein (72 kD type IV collagenase) in primary skin melanoma. J Path 186: 51-58, 1998Google Scholar
  7. 7.
    Kodate M, Kasai T, Hashimoto H, Yasumoto K, Iwata Y, Manabe H: Expression of MMP (gelatinase) in T1 adenocarcinoma of the lung. Pathol Int 47: 461-469, 1997Google Scholar
  8. 8.
    Monteagudo C, Merino MJ, San-Juan J, Liotta LA, Stetler-Stevenson WG: Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue. Am J Pathol 136: 585-592, 1990Google Scholar
  9. 9.
    Davies B, Miles DW, Happerfield LC, Naylor MS, Bobrow LG, Rubens RD, Balkwill FR: Activity of type IV collagenases in benign and malignant breast disease. Br J Cancer 67: 1126-1131, 1993Google Scholar
  10. 10.
    Tryggvason K, Höyhtyä M, Pyke C: Type IV collagenases in invasive tumours. Breast Cancer Res Treat 24: 209-218, 1993Google Scholar
  11. 11.
    Daidone MG, Silvestrini R, D'Errico A, Di Fronzo G, Benini E, Mancini WG, Garbisa S, Liotta LA, Grigioni WF: Laminin receptors, collagenase IV and prognosis in node-negative breast cancers. Int J Cancer 48: 529-532, 1991Google Scholar
  12. 12.
    Höyhtyä M, Fridman R, Komarck D, Porter-Jordan K, Stetler-Stevenson NG, Liotta LA, Liang CM: Immunohistochemical localization of matrix metalloproteinase 2 and its specific inhibitor TIMP-2 in neoplastic tissue with monoclonal antibodies. Int J Cancer 54: 500-505, 1994Google Scholar
  13. 13.
    Kurizaki T, Toi M, Tominaga T: Relationship between matrix metalloproteinase expression and tumor angiogenesis in human breast carcinoma. Oncology Reports 5(3): 673-677, 1998Google Scholar
  14. 14.
    Talvensaari-Mattila A, Pääkkö P, Höyhtyä M, Blanco-Sequeiros G, Turpeenniemi-Hujanen T: Matrix metalloproteinase-2 immunoreactive protein, a marker of aggressiveness in breast carcinoma. Cancer 83: 1153-1162, 1998Google Scholar
  15. 15.
    Hermanek P, Sobin LH, (eds): UICC TNM Classification of malignant tumours 4th edn 2nd rev. Berlin: Springer-Verlag, 1992Google Scholar
  16. 16.
    Scarff RW, Torloni H: Histological typing of breast tumours. WHO: Geneva, 1986Google Scholar
  17. 17.
    Bloom HJG, Richardson WW: Histological grading and prognosis in breast cancer. Br J Cancer 11: 359-377, 1957Google Scholar
  18. 18.
    Hsu SM, Raine L, Fanger H: The use of avidin-biotinperoxidase complex (ABC) in immunoperoxidase technique: A comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29: 577-580, 1981Google Scholar
  19. 19.
    Marqulies IMK, Höyhtyä M, Evans C, Stracke ML, Liotta LA, Stetler-Stevenson WG: Urinary type IV collagenase elevated levels are associated with bladder transitional cell carcinoma. Cancer Epidemiol Biomark Prev 467-474, 1992Google Scholar
  20. 20.
    Väisänen A, Tuominen H, Kallioinen M, Turpeenniemi-Hujanen T: Matrix metalloproteinase-2 (72 kD type IV collagenase) expression occurs in the early stage of human melanocytic tumour progression and may have prognostic value. J Pathol 180: 283-289, 1996Google Scholar
  21. 21.
    Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457-481, 1958Google Scholar
  22. 22.
    Mantel N: Evaluation of survival data and two new rank order statistics arising in this consideration. Cancer Chemother Rep 50: 163-170, 1966Google Scholar
  23. 23.
    Norton L: A compertzian model of human breast cancer growth. Cancer Res 48: 7067-7071, 1988Google Scholar
  24. 24.
    D'Errico A, Garbisa S, Liotta LA, Castronovo V, Stetler-Stevenson WG, Griogioni WG: Augmentation of type IV collagenase, lamin in receptor, and Ki67 proliferation antigen associated with human colon, gastric, and breast carcinoma progression. Med Pathol 4: 239-246, 1991Google Scholar
  25. 25.
    Campo E, Tavassoli FA, Charonis AS, Stetler-Stevenson WG, Liotta LA, Merino MJ: Evaluation of basement membrane components and the 72KDa type IV collagenase in serous tumours of the ovary. Am J Pathol 6: 500-507, 1992Google Scholar
  26. 26.
    Visscher DW, Höyhtyä M, Ottosen SK, Liang C-M, Sarkar FH, Crissman JD: Enhanced expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) in stroma of breast carcinomas correlates with tumour recurrence. Int J Cancer 59: 339-344, 1994Google Scholar
  27. 27.
    Ueno H, Nakamura H, Inoue M, Imai K, Noguchi M, Sato H, Seiki M, Okada Y: Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in human invasive breast carcinomas. Cancer Res 57: 2055-2060, 1997Google Scholar
  28. 28.
    Soini Y, Hurskainen T, Höyhtyä M, Oikarinen A, Autio-Harmainen H: 72KD and 92KD type IV collagenase, type IV collagen, and laminin mRNAs in breast cancer: a study by in situ hybridization. J Histochem Cytochem 42: 945-951, 1994Google Scholar
  29. 29.
    Väisänen A, Kallioinen M, von Dickhoff K, Laatikainen L, Höyhtyä M, Turpeenniemi-Hujanen T: Matrix metalloproteinase-2 (MMP-2) immunoreactive protein-a new prognostic marker in uveal melanoma? J Pathol 188: 56-62, 1999Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • A. Talvensaari-Mattila
    • 1
  • P. Pääkkö
    • 2
  • G. Blanco-Sequeiros
    • 1
  • T. Turpeenniemi-Hujanen
    • 1
  1. 1.Department of Oncology and RadiotherapyUniversity of Oulu and Oulu University HospitalOuluFinland
  2. 2.Department of PathologyUniversity of Oulu and Oulu University HospitalOuluFinland

Personalised recommendations