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Comparison of monoclonal antibodies for the detection of occult breast carcinoma metastases in bone marrow

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Summary

Twenty percent (n = 6) of Stage III or IV breast cancer patients (n = 30) had bone marrow metastases detected in bilateral bone marrow biopsy/aspiration preparations using standard histologic preparations. Each metastasis was also detected by four separate monoclonal antibodies (MAbs) which recognize breast carcinoma associated antigens (DF3, anti-EMA, HMFG-2, and CAM5.2). These MAbs were then utilized to stain other bone marrow preparations (n = 81) to determine their utility for the detection of micrometastatic breast carcinoma. MAbs HMFG-2, anti-EMA, and DF3 were each strongly reactive with bone marrows containing histologically-evident metastatic breast carcinoma (18/18). These anti-epithelial membrane antigen MAbs, however, were also reactive with rare plasma cells and immature cells (as well as cell clusters) in some of the control bone marrow samples tested, including those from normal patients and patients with hematologic disorders. They also reacted with some of the preparations from patients with leukemia and lymphoma, and with uninvolved marrows from patients with non-epithelial malignancies. The anti-keratin MAb CAM5.2, in contrast, reacted with 83% (15/18) breast cancer metastases and failed to stain any cells in the various categories of control marrow preparations. These data suggested that MAb CAM5.2 might be utilized to immunohistochemically differentiate micrometastatic breast carcinoma from immature myeloid or erythroid elements.

Each MAb was then reacted with histologically uninvolved marrow preparations from the remaining 24 of 30 breast cancer patients in an attempt to identify occult breast carcinoma metastases. While MAbs HMFG-2, DF3, and anti-EMA demonstrated reactive cells in some of these marrows, this reactivity was similar to that seen with control preparations. MAb CAM5.2, in contrast, was negative with all specimens. These data suggest that MAb CAM5.2 may be a useful immunologic probe for the detection and confirmation of metastatic breast carcinoma in bone marrow, while more caution must be employed in the interpretation of results obtained using MAbs anti-EMA, DF3, and HMFG-2.

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References

  1. Harris JR, Hellman S, Canellos GP, Fisher B: Cancer of the breast. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer Principles and Practice. J.B. Lippincott Co., Philadelphia, 1985, pp 1119–1177

    Google Scholar 

  2. Dicke KA, Spitzer G: Evaluation of the use of high dose cytoreduction with autologous bone marrow rescue in various malignancies. Transplantation 41: 4–20, 1986

    PubMed  Google Scholar 

  3. Sahir O, Parker ML: Metastases of primary carcinoma of the breast with special reference to spleen, adrenal glands and ovaries. Arch Surg 42: 1003–1018, 1941

    Google Scholar 

  4. Haagensen CD: Diseases of the Breast, 2nd ed. WB Saunders, Philadelphia, 1971

    Google Scholar 

  5. Redding WH, Monaghan P, Imrie SF, Omerod MG, Gazet J-C, Coombes RC, Clink H McD, Dearnaley DP, Sloane JP, Powles TJ, Neville AM: Detection of micrometastases in patients with primary breast cancer. Lancet ii: 1271–1273, 1983

    Google Scholar 

  6. Tagnon HJ: Some changing concepts of the natural history of human mammary cancer and their effect on diagnosis and treatment. Eur J Cancer 22: 123–128, 1986

    Google Scholar 

  7. Lippman ME: The NIH concensus development conference on adjuvant chemotherapy for breast cancer — a commentary. Breast Cancer Res Treat 6: 195–200, 1985

    PubMed  Google Scholar 

  8. Sloane JP, Ormerod MG, Imrie S, Coombes RC: The use of antisera to epithelial membrane antigen in detecting micrometastases in histologic sections. Br J Cancer 42: 392–398, 1980

    PubMed  Google Scholar 

  9. Dearnaley DP, Sloane JP, Imrie S, Coombes RC, Ormerod MG, Lumley H, Jones M, Neville AM: Detection of isolated mammary carcinoma cells in marrow of patients with primary breast cancer. J Roy Soc Med 76: 359–364, 1983

    Google Scholar 

  10. Dearnaley DP, Sloane JP, Ormerod MG, Steele K, Coombes RC, Clink H McD, Paules TJ, Ford HT, Gazet J-T, Neville AM: Increased detection of mammary carcinoma cells in marrow smears using antisera to epithelial membrane antigen. Br J Cancer 44: 85–90, 1981

    PubMed  Google Scholar 

  11. Ghosh AK, Erber WN, Hatten CSR, O'Connor NTJ, Falini B, Osborn M, Mason DY: Detection of metastatic tumor cells in routine bone marrow smears by immunoalkaline phosphatase labelling with monoclonal antibodies. Br J Haematology 61: 21–30, 1985

    Google Scholar 

  12. Pinkus GS, Kurtin P: Epithelial membrane antigen — a diagnostic discriminant in surgical pathology: Immunohistochemical profile in epithelial, mesenchymal and hematopoietic neoplasms using paraffin sections and monoclonal antibodies. Human Pathol 6: 929–940, 1985

    Google Scholar 

  13. To A, Coleman DV, Dearnaley DP, Ormerod MG, Steele K, Neville AM: Use of antisera to epithelial membrane antigen for the cytodiagnosis of malignancy in serous effusions. J Clin Pathol 34: 1326–1332, 1981

    PubMed  Google Scholar 

  14. Hilborne LH, Cheng L, Nieberg RK, Lewin KJ: Evaluation of an antibody to human milk fat globule antigen in the detection of metastatic carcinoma in pleural, pericardial, and peritoneal fluids. Acta Cytol 30: 245–250, 1986

    PubMed  Google Scholar 

  15. Kufe D, Inghirami G, Abe M, Hayes D, Justi-Wheeler H, Schlom J: Differential reactivity of a novel monoclonal antibody (DF3) with human malignant versus benign breast tumors. Hybridoma 3: 223–232, 1984

    PubMed  Google Scholar 

  16. Sekine H, Tsureya O, Kufe DW: Purification and characterization of a high molecular weight glycoprotein detectable in human milk and breast carcinomas. J Immunol 135: 3610–3615, 1985

    PubMed  Google Scholar 

  17. Heyderman E, Steele K, Ormerod MG: A new antigen on the epithelial membrane: its immunoperoxidase localization in normal and neoplastic tissue. J Clin Pathol 32: 35–9, 1979

    PubMed  Google Scholar 

  18. Ormerod MG, Steele K, Westwood JH, Mazzini MN: Epithelial membrane antigen: partial purification, assay, and properties. Br J Cancer 48: 533–541, 1983

    PubMed  Google Scholar 

  19. Burchell J, Durbin H, Taylor-Papadimitriou J: Complexity of expression of antigenic determinants, recognized by monoclonal antibodies HMFG-1 and HMFG-2, in normal and malignant human mammary epithelial cells, J Immunol 131: 508–513, 1983

    PubMed  Google Scholar 

  20. Taylor-Papadimitriou J, Peterson JA, Arklie J, Burchell J, Ceriani RL, Bodmer WF: Monoclonal antibodies to epithelium specific components of the milk fat globule membrane: production and reaction with cells. Int J Cancer 28: 17–21, 1981

    PubMed  Google Scholar 

  21. Moll R, Franke WW, Schiller DL, Gieger B, Krepler K: The catalog of human cytokeratins: Patterns of expression in normal epithelia, tumors and cultured cells. Cell 31: 11–24, 1982

    PubMed  Google Scholar 

  22. Makin CA, Bobrow LG, Bodmer WF: Monoclonal antibody to cytokeratin for use in routine histopathology. J Clin Pathol 37: 975–983, 1984

    PubMed  Google Scholar 

  23. Potter M: Immunoglobulin-producing tumors and myeloma proteins of mice. Physiol Rev 52: 631–719, 1972

    PubMed  Google Scholar 

  24. Johnston WW, Szpak CA, Lottich SC, Thor A, Schlom J: Use of a monoclonal antibody (B72.3) as an immunocytochemical adjunct to diagnosis of adenocarcinoma in human effusions. Cancer Res 45: 1894–1900, 1985

    PubMed  Google Scholar 

  25. Martin SE, Moshiri S, Thor A, Vilasi V, Chu EW, Schlom J: Identification of adenocarcinoma in cytospin preparations of effusions using monoclonal antibody B72.3. Am J Clin Pathol 86: 10–18, 1986

    PubMed  Google Scholar 

  26. Nuti M, Mottolese M, Viora M, Perrone Donnorso R, Schlom J, Natali PG: Use of monoclonal antibodies to human breast-tumor-associated antigens in fine-needle aspirate cytology. Int J Cancer 37: 493–498, 1986

    PubMed  Google Scholar 

  27. Hsu SM, Raine L, Fanger H: Use of avidin-biotin complex (ABC) in immunoperoxidase techniques: Comparison between ABC and unlabelled antibody (PAP) procedure. J Histochem Cytochem 29: 577–580, 1981

    PubMed  Google Scholar 

  28. Thor A, Gorstein F, Ohuchi N, Szpak CA, Johnston WW, Schlom J: Tumor-associated glycoprotein (TAG-72) in ovarian carcinomas defined by monoclonal antibody B72.3. J Natl Cancer Inst 76: 995–1005, 1986

    PubMed  Google Scholar 

  29. Bussolati G, Gugliotta P: Non-specific staining of mast cells by avidin biotin peroxidase complexes (ABC). J Histochem Cytochem 31: 1419–1421, 1983

    PubMed  Google Scholar 

  30. Shimizu M, Yamauchi K: Isolation and characterization of mucin-like glycoprotein in human milk fat globule membrane. J Bioch 91: 515–24, 1982

    Google Scholar 

  31. Berry N, Jones DB, Smallwood J, Taylor I, Kirkham N, Taylor-Papadimitriou J: The prognostic value of monoclonal antibodies HMFG-1 and HMFG-2 in breast cancer. Br J Cancer 51: 179–186, 1985

    PubMed  Google Scholar 

  32. Lundy J, Thor A, Maenza R, Schlom J, Forouhar F, Testa M, Kufe D: Monoclonal antibody DF3 correlates with tumor differentiation and hormone receptor status in breast Cancer patients. Breast Cancer Res Treat 5:269–276, 1985

    PubMed  Google Scholar 

  33. Sloane JP, Hughes F, Ormerod MG: An assessment of the value of EMA and other epithelial markers in solving diagnostic problems in tumor histopathology. Histochem J 15: 645–654, 1983

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Tumor Immunology and Biology, NIH, NCI, Building 10, Room 8B07, 20892, Bethesda, MD, USA

    Ann Thor, Mary Jo Viglione, Noriaki Ohuchi, Jean Simpson & Jeffrey Schlom

  2. Howard Hughes Medical Institute, 20892, Bethesda, MD, USA

    Mary Jo Viglione

  3. Medical Breast Cancer Section, Medicine Branch, NIH, NCI, 20892, Bethesda, MD, USA

    Ronald Steis & Marc Lippman

  4. Department of Pathology, Vanderbilt University Hospital, 37232, Nashville, TN, USA

    John Cousar

  5. Dana-Farber Cancer Institute, 02115, Boston, MA, USA

    Donald W. Kufe

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  1. Ann Thor
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  2. Mary Jo Viglione
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  3. Noriaki Ohuchi
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  4. Jean Simpson
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  7. Marc Lippman
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  8. Donald W. Kufe
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  9. Jeffrey Schlom
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Thor, A., Viglione, M.J., Ohuchi, N. et al. Comparison of monoclonal antibodies for the detection of occult breast carcinoma metastases in bone marrow. Breast Cancer Res Tr 11, 133–145 (1988). https://doi.org/10.1007/BF01805837

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