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. 1994 Jun;69(6):1126–1129. doi: 10.1038/bjc.1994.221

Immunodetection of bone marrow micrometastases in breast carcinoma patients and its correlation with primary tumour prognostic features.

S Ménard 1, P Squicciarini 1, A Luini 1, V Sacchini 1, D Rovini 1, E Tagliabue 1, P Veronesi 1, B Salvadori 1, U Veronesi 1, M I Colnaghi 1
PMCID: PMC1969436  PMID: 7911032

Abstract

Methods such as immunohistochemistry that have enhanced the detection of carcinoma cells in bone marrow aspirates appear to be useful in identifying patients with aggressive tumours. To detect epithelial cells in bone marrow aspirates from breast carcinoma patients, we used a pool of five different monoclonal antibodies (MAbs), which recognise 100% of breast carcinomas, together with the alkaline phosphatase method on cytospun cells obtained from sternum and iliac crest. Primary tumours were also analysed for the expression of the c-erbB-1 and c-erbB-2 oncogene products, and of two differentiation-related markers and laminin receptors. Immunoreactive cells were detected in the bone marrow of 62 of the 197 patients tested (31%) without any correlation with clinical parameters such as tumour size or lymph node metastasis, whereas a significant (P < 0.01) correlation was found with enhanced monomeric laminin receptor expression in the primary tumour. In fact, this receptor was expressed in respectively 63% and 38% of primary tumours from patients with and without immunoreactive cells in the bone marrow aspirates. Thus, the presence of immunoreactive cells in bone marrow correlates with the expression in the primary tumour of a marker of the metastatic potential of the tumour, the 67 kDa laminin receptor.

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Selected References

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  1. Bottini C., Miotti S., Fiorucci S., Facheris P., Ménard S., Colnaghi M. I. Polarization of the alpha 6 beta 4 integrin in ovarian carcinomas. Int J Cancer. 1993 May 8;54(2):261–267. doi: 10.1002/ijc.2910540217. [DOI] [PubMed] [Google Scholar]
  2. Cote R. J., Rosen P. P., Hakes T. B., Sedira M., Bazinet M., Kinne D. W., Old L. J., Osborne M. P. Monoclonal antibodies detect occult breast carcinoma metastases in the bone marrow of patients with early stage disease. Am J Surg Pathol. 1988 May;12(5):333–340. doi: 10.1097/00000478-198805000-00001. [DOI] [PubMed] [Google Scholar]
  3. Dearnaley D. P., Ormerod M. G., Sloane J. P. Micrometastases in breast cancer: long-term follow-up of the first patient cohort. Eur J Cancer. 1991;27(3):236–239. doi: 10.1016/0277-5379(91)90504-7. [DOI] [PubMed] [Google Scholar]
  4. Dearnaley D. P., Sloane J. P., Ormerod M. G., Steele K., Coombes R. C., Clink H. M., Powles T. J., Ford H. T., Gazet J. C., Neville A. M. Increased detection of mammary carcinoma cells in marrow smears using antisera to epithelial membrane antigen. Br J Cancer. 1981 Jul;44(1):85–90. doi: 10.1038/bjc.1981.152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ellis G., Ferguson M., Yamanaka E., Livingston R. B., Gown A. M. Monoclonal antibodies for detection of occult carcinoma cells in bone marrow of breast cancer patients. Cancer. 1989 Jun 15;63(12):2509–2514. doi: 10.1002/1097-0142(19890615)63:12<2509::aid-cncr2820631225>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  6. Facheris P., Perrone F., Ménard S., Andreola S., Bazzini P., Bufalino R., Canevari S., Cascinelli N., Colzani E., Di Fronzo G. Study of the biological and prognostic significance of the antigen CaMBr8 on breast carcinoma. Br J Cancer. 1992 Mar;65(3):466–470. doi: 10.1038/bjc.1992.94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kallioniemi O. P., Holli K., Visakorpi T., Koivula T., Helin H. H., Isola J. J. Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer. 1991 Nov 11;49(5):650–655. doi: 10.1002/ijc.2910490504. [DOI] [PubMed] [Google Scholar]
  8. Mansi J. L., Berger U., Easton D., McDonnell T., Redding W. H., Gazet J. C., McKinna A., Powles T. J., Coombes R. C. Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases. Br Med J (Clin Res Ed) 1987 Oct 31;295(6606):1093–1096. doi: 10.1136/bmj.295.6606.1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mariani-Costantini R., Barbanti P., Colnaghi M. I., Ménard S., Clemente C., Rilke F. Reactivity of a monoclonal antibody with tissues and tumors from the human breast. Immunohistochemical localization of a new antigen and clinicopathologic correlations. Am J Pathol. 1984 Apr;115(1):47–56. [PMC free article] [PubMed] [Google Scholar]
  10. Martignone S., Ménard S., Bufalino R., Cascinelli N., Pellegrini R., Tagliabue E., Andreola S., Rilke F., Colnaghi M. I. Prognostic significance of the 67-kilodalton laminin receptor expression in human breast carcinomas. J Natl Cancer Inst. 1993 Mar 3;85(5):398–402. doi: 10.1093/jnci/85.5.398. [DOI] [PubMed] [Google Scholar]
  11. Martignone S., Pellegrini R., Villa E., Tandon N. N., Mastroianni A., Tagliabue E., Ménard S., Colnaghi M. I. Characterization of two monoclonal antibodies directed against the 67 kDa high affinity laminin receptor and application for the study of breast carcinoma progression. Clin Exp Metastasis. 1992 Nov;10(6):379–386. doi: 10.1007/BF00133466. [DOI] [PubMed] [Google Scholar]
  12. Pellegrini R., Bazzini P., Tosi E., Tagliabue E., Conforti G., Dejana E., Ménard S., Colnaghi M. I. Production and characterization of two monoclonal antibodies directed against the integrin beta 1 chain. Tumori. 1992 Feb 29;78(1):1–4. doi: 10.1177/030089169207800101. [DOI] [PubMed] [Google Scholar]
  13. Pellegrini R., Centis F., Martignone S., Mastroianni A., Tagliabue E., Tosi E., Ménard S., Colnaghi M. I. Characterization of a monoclonal antibody directed against the epidermal growth factor receptor binding site. Cancer Immunol Immunother. 1991;34(1):37–42. doi: 10.1007/BF01741322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Porro G., Ménard S., Tagliabue E., Orefice S., Salvadori B., Squicciarini P., Andreola S., Rilke F., Colnaghi M. I. Monoclonal antibody detection of carcinoma cells in bone marrow biopsy specimens from breast cancer patients. Cancer. 1988 Jun 15;61(12):2407–2411. doi: 10.1002/1097-0142(19880615)61:12<2407::aid-cncr2820611202>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  15. Riethmüller G., Johnson J. P. Monoclonal antibodies in the detection and therapy of micrometastatic epithelial cancers. Curr Opin Immunol. 1992 Oct;4(5):647–655. doi: 10.1016/0952-7915(92)90041-c. [DOI] [PubMed] [Google Scholar]
  16. Sager R., Anisowicz A., Neveu M., Liang P., Sotiropoulou G. Identification by differential display of alpha 6 integrin as a candidate tumor suppressor gene. FASEB J. 1993 Jul;7(10):964–970. doi: 10.1096/fasebj.7.10.8344495. [DOI] [PubMed] [Google Scholar]
  17. Salvadori B., Squicciarini P., Rovini D., Orefice S., Andreola S., Rilke F., Barletta L., Menard S., Colnaghi M. I. Use of monoclonal antibody MBr1 to detect micrometastases in bone marrow specimens of breast cancer patients. Eur J Cancer. 1990;26(8):865–867. doi: 10.1016/0277-5379(90)90185-v. [DOI] [PubMed] [Google Scholar]
  18. Schlimok G., Funke I., Holzmann B., Göttlinger G., Schmidt G., Häuser H., Swierkot S., Warnecke H. H., Schneider B., Koprowski H. Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8672–8676. doi: 10.1073/pnas.84.23.8672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Stahel R. A., Mabry M., Skarin A. T., Speak J., Bernal S. D. Detection of bone marrow metastasis in small-cell lung cancer by monoclonal antibody. J Clin Oncol. 1985 Apr;3(4):455–461. doi: 10.1200/JCO.1985.3.4.455. [DOI] [PubMed] [Google Scholar]
  20. Tagliabue E., Centis F., Campiglio M., Mastroianni A., Martignone S., Pellegrini R., Casalini P., Lanzi C., Ménard S., Colnaghi M. I. Selection of monoclonal antibodies which induce internalization and phosphorylation of p185HER2 and growth inhibition of cells with HER2/NEU gene amplification. Int J Cancer. 1991 Apr 1;47(6):933–937. doi: 10.1002/ijc.2910470625. [DOI] [PubMed] [Google Scholar]
  21. Tagliabue E., Porro G., Barbanti P., Della Torre G., Ménard S., Rilke F., Cerasoli S., Colnaghi M. I. Improvement of tumor cell detection using a pool of monoclonal antibodies. Hybridoma. 1986 Summer;5(2):107–115. doi: 10.1089/hyb.1986.5.107. [DOI] [PubMed] [Google Scholar]
  22. Zutter M. M., Krigman H. R., Santoro S. A. Altered integrin expression in adenocarcinoma of the breast. Analysis by in situ hybridization. Am J Pathol. 1993 May;142(5):1439–1448. [PMC free article] [PubMed] [Google Scholar]

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