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Expression of gelatinases A and B, stromelysin-3 and matrilysin genes in breast carcinomas: clinico-pathological correlations

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Abstract

The purpose of this study was to investigate the association among matrix metalloproteinases (gelatinases A and B, stromelysin-3 (ST3) and matrilysin) mRNAs expressed in primary breast carcinomas and stan-dard prognostic parameters and clinical outcome. mRNA levels were determined by Northern analysis in samples of 81 breast cancer patients (median follow-up, 40 months) and 27 samples of uninvolved adjacent breast tissue. Proteases were expressed by the majority of the tumors and normal breast tissues examined. ST3, gelatinase A and matrilysin mRNAs were more often expressed at high levels in carcinomatous than in normal breast tissues. Differences in the distribution of gelatinase B mRNA were not found. However, paired normal tissues generally produced weaker signals when compared to matched tumor samples. Univariate analysis showed no significant association of gelatinase A and matrilysin mRNAs with the classical prognostic markers (age, menopausal status, stage, size, nodal status, vascular infiltrate, necrosis, steroid receptors, metastasis and survival). Overexpression of ST3 was more frequently found in tumors of post-menopausal women (P < 0.022). Elevated expression of gel B mRNA was associated with the presence of vascular infiltrate (P < 0.026), necrosis (P < 0.039), PR negative tumors (P < 0.014) and inversely corre-lated to the number of survivors (P < 0.021). Multivariate analysis including 68 patients for whom all information was available indicated that neither stromelysin correlated significantly with pathological, clin-ical or biochemical features. High levels of gelatinase A and B mRNAs were inversely associated with the number of survivors. Our findings suggest that measurements of gelatinase A and B mRNAs expression in breast carcinoma may help to identify patients with an agressive form of the disease. ©Lippincott Williams & Wilkins

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References

  1. Duffy MJ, 1996, Proteases as prognostic markers in cancer. Clin Cancer Res, 2, 613-18.

    Google Scholar 

  2. Wolf C, Rouyer N, Lutz Y et al.,1993, Stromelysin 3 belongs to a subgroup of proteinases expressed in breast carcinoma fibroblastic cells and possibly implicated in tumor progression. Proc Natl Acad Sci USA,90, 1843-47.

    Google Scholar 

  3. Monteagudo C, Merino MJ, San-Juan J et al.,1990, Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue. Am J Pathol, 136, 585-92.

    Google Scholar 

  4. Daidone MG, Silvestrini R, D'Errico A et al.,1991, Laminin receptors, collagenase IV and prognosis in node-negative breast cancer. Int J Cancer, 48, 529-32.

    Google Scholar 

  5. Brown PD, Bloxidge RE, Anderson E and Howell A, 1993, Expression of activated gelatinase in human invasive breast carcinoma. Clin Exp Met, 11, 183-9. 11111

    Google Scholar 

  6. Davies B, Miles DW, Happerfield LC et al.,1993, Activity of type IV collagenases in benign and malignant breast tissue disease. Br J Cancer, 67, 1126-31.

    Google Scholar 

  7. Polette M, Gilbert N, Stas I et al.,1994, Gelatinase A expression and localization in human breast cancers. An in situ hybridization study and immunohistochemical detection using confocal microscopy. Virchows Archiv, 424, 641-5.

    Google Scholar 

  8. Visscher DW, Höyhtyä M, Ottosen SK et al.,1994, Enhanced expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) in the stroma of breast carcinomas correlates with tumor recurrence. Int J Cancer, 59, 339-44.

    Google Scholar 

  9. Duffy MJ, Blaser J, Duggan C et al., 1995, Assay of matrix metalloproteases types 8 and 9 by ELISA in human breast cancer. Br J Cancer, 71, 1025-8.

    Google Scholar 

  10. Lee KS, Rha SY, Kim JH et al., 1996, Sequential activation and production of matrix metalloproteinase-2 during breast cancer progression. Clin Exp Metastasis,14, 512-9.

    Google Scholar 

  11. Chambers AF and Matrisian LM, 1997, Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst, 89, 1260-70.

    Google Scholar 

  12. Rio MC, Lefebvre O, Santavicca M et al., 1996, Stromelysin-3 in the biology of the normal and neo-plastic mammary gland. J Mamm Gland Biol Neo, 1, 231-40.

    Google Scholar 

  13. Heppner KJ, Matrisian LM, Jensen RA and Rodgers WH, 1996, Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am J Pathol, 149, 273-82.

    Google Scholar 

  14. Hähnel E, Harvey JM, Joyce R et al., 1993, Stromelysin-3 expression in breast cancer biopsies: clinico-pathological correlations. Int J Cancer, 55, 771-4.

    Google Scholar 

  15. Santavicca M, Noël A, Chenard M-P et al., 1995, Characterization of monoclonal antibodies against stromelysin-3 and their use to evaluate stromelysin-3 levels in breast carcinoma by semi-quantitative immunohistochemistry. Int J Cancer, 64, 336-41.

    Google Scholar 

  16. Basset P, Belloq JP, Wolf C et al., 1990, A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature, 348, 699-704.

    Google Scholar 

  17. Collier IE, Wilhelm SM and Eisen AZ, 1988, H-ras oncogene-transformed human bronchial ephitelial cells (TBE-1) secrete a single metalloprotease capable of degradating basemant membrane collagen. J Biol Chem, 263, 6579-87.

    Google Scholar 

  18. Wilhelm SM, Collier IE, Marmer BL et al., 1989, SV40-transformed human lung fibroblasts secrete a 92-kDa collagenase which is identical to that secreted by normal human macrophages. J Biol Chem, 264, 17213-21.

    Google Scholar 

  19. Muller D, Quantin B, Geshel MC et al., 1988, The collagenase gene family in humans consistis of a least four members. Biochem J, 253, 187-92.

    Google Scholar 

  20. Arnhein N, 1979, Characterization of mouse ribosomal gene fragments purified by molecular clone. Gene, 72, 83-96.

    Google Scholar 

  21. Chomczynski P and Sacchi N, 1987, Single-step method of RNA isolation by acid guanidinium thiocyanatephenol-chloroform extration. Anal Biochem, 162, 156-9.

    Google Scholar 

  22. Fourney RM, Miyashi J, Day III RS and Paterson MC, 1988, Northern blotting: efficient RNA staining and transfer. Focus, 10, 5-7.

    Google Scholar 

  23. Pacheco MM, Brentani MM, Franco EL et al., 1988, Plasminogen activator expression and steroid hormone receptors in female breast cancer: a multi-factorial study. Int J Cancer, 41, 798-804.

    Google Scholar 

  24. Kawami H, Yoshida K, Ohsaki A et al., 1993, Stromelysin-3 mRNA expression and malignancy: comparison with clinicopathological features and type IV collagenase mRNA expression in breast tumors. Anticancer Res, 13, 2319-24.

    Google Scholar 

  25. Engel G, Heselmeyer K, Auer G et al., 1994, Correlation between stromelysin-3 mRNA level and outcome of human breast cancer. Int J Cancer, 58, 830-5.

    Google Scholar 

  26. Chenard M-P, O'Siorain L, Shering S et al., 1996, High levels of stromelysin-3 correlate with poor prognosis in patients with breast carcinoma. Int J Cancer, 69, 448-51.

    Google Scholar 

  27. Kossakowska AE, Huchcroft SA, Urbanski SJ and Edwards DR, 1996, Comparative analysis of the expression patterns of metalloproteinases and their inhibitors in breast neoplasia, sporadic colorectal neoplasia, pulmonary carcinomas and malignant non-Hodgkin's lymphomas in humans. Br J Cancer, 73, 1401-8.

    Google Scholar 

  28. Singer CF, Rasmussen A, Lippman ME and Cullen KJ, 1997, Coexpression of stromelysin-3 and insulin-like growth factor II in tumors of ectodermal, mesodermal, and endodermal origin: Indicator of a fetal cell phenotype. J Clin Endocrinol Metab, 82, 1917-22.

    Google Scholar 

  29. Basset P, Wolf C, Rouyer N et al., 1994, Stromelysin-3 in stromal tissue as a control factor in breast cancer behavior. Cancer ( Suppl ), 74, 1045-9.

    Google Scholar 

  30. Noël AC, Lefebvre O, Maquoi E et al., 1996, Stromelysin-3 expression promotes tumor take in nude mice. J Clin Invest, 97, 1924-30.

    Google Scholar 

  31. Ahmad A, Marshall JF, Basset P et al., 1997, Modulation of human stromelysin 3 promotes activity and gene expression by human breast cancer cells. Int J Cancer, 73, 290-6.

    Google Scholar 

  32. MacDougall JR, Rudolph LA, Arteaga C and Matrisian LM, 1997, Expression of the metalloproteinase matrilysin is regulated by both positive and negative factors in breast cancer cells. Proc Am Assoc Cancer Res, 38, 405.

    Google Scholar 

  33. Onisto M, Riccio MP, Scannapieco P et al., 1995, Gelatinase A/TIMP-2 imbalance in lymph-node-positive breast carcinomas, as measured by RT-PCR. Int J Cancer, 63, 621-6.

    Google Scholar 

  34. Ree AH, Florenes VA, Berg JP et al., 1997, High levels of messenger RNAs for tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in primary breast carcinomas are associated with development of distant metastases. Clin Cancer Res, 3, 1623-28.

    Google Scholar 

  35. Zucker S, Lysik RM, Zarrabi MH and Moll U, 1993, Mr 92,000 types IV collagenase is increased in plasma of patients with colon cancer and breast cancer. Cancer Res, 53, 140-6.

    Google Scholar 

  36. Soini Y, Hurskainen T, Hoyhtya M et al.,1994, 72 kD and 92 kD type IV collagenase, type IV collagen and laminin mRNAs in breast cancer: a study by in situhybridization. J Histochem Cytochem, 42, 945-51.

    Google Scholar 

  37. Nielsen BS, Sehested M, Kjeldsen L et al., 1997, Expression of matrix metalloprotease-9 in vascular pericytes in human breast cancer. Lab Invest, 77, 345-55.

    Google Scholar 

  38. Mantovani A, 1994, Tumor-associated macrophages in neoplastic progression: A paradigm for the in vivo function of chemokines. Lab Invest, 71, 5-16.

    Google Scholar 

  39. Matrisian LM, 1990, Metalloproteinases and their inhibitors in matrix remodelling. Trends Genet, 6, 121-5.

    Google Scholar 

  40. Emonard HP, Ramacle AG, Noel AC et al.,1992, Tumour cell surface-associated binding site for the Mr 72,000 type IV collagenase. Cancer Res, 52, 5845-8.

    Google Scholar 

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Authors and Affiliations

  1. Divisao de Oncologia Clínica e Laboratorial, Fundacao Oncocentro de Sao Paulo, Sao Paulo-SP, Brasil

    Mercia M Pacheco

  2. Departamento de Mastologia, Hospital A. C. Camargo, Sao Paulo-SP, Brasil

    Mario Mourao & Ines N Nishimoto

  3. Servico de Mastologia, Instituto Brasileiro de Controle do Cancer, Sao Paulo-SP, Brasil

    Edson B Mantovani & M Mitzi Brentani

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  1. Mercia M Pacheco
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  2. Mario Mourao
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  4. Ines N Nishimoto
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  5. M Mitzi Brentani
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Pacheco, M.M., Mourao, M., Mantovani, E.B. et al. Expression of gelatinases A and B, stromelysin-3 and matrilysin genes in breast carcinomas: clinico-pathological correlations. Clin Exp Metastasis 16, 577–585 (1998). https://doi.org/10.1023/A:1006580415796

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