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Disseminated Epithelial Tumor Cells in Bone Marrow of Patients with Esophageal Cancer: Detection and Prognostic Significance

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Abstract

Minimal residual disease in patients with operable esophageal cancer is frequently missed by current noninvasive tumor staging. Here we applied an immunocytochemical cytokeratin assay that allows identification of individual esophageal carcinoma cells disseminated to bone marrow. Prior to therapy, bone marrow was aspirated from the upper iliac crest of 71 patients with esophageal cancer at various disease stages as well as an age-matched control group of 20 noncarcinoma patients. Tumor cells in cytologic bone marrow preparations were detected with monoclonal antibodies (mAbs) CK2, KL1, and A45-B/B3 to epithelial cytokeratins (CKs) using the alkaline phosphatase antialkaline phosphatase method. CK-positive cells were found in 14 (36.8%) of 38 cancer patients treated with curative intent and 16 (48.5%) of 33 patients with extended disease. The overall frequency of these cells was 1 per 4 × 105 to 82 per 4 × 105 mononuclear cells with no significant differences between patients at different tumor stages. After a short median follow-up of 9.5 months (3–24 months), 7 of 11 patients who underwent complete surgical resection but had tumor cells in bone marrow presented with tumor relapse compared to 2 of 19 corresponding patients without such cells (p < 0.01). It was concluded that although bone marrow is not a preferential site of overt metastasis of esophageal cancer, the frequent occurrence of isolated tumor cells at this distant site indicates that hematogenous dissemination of viable malignant cells occurs early in tumor progression.

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References

  1. Siewert, J.R., Roder, J., Fink, U.: Fortschritte in der chirugischen Behandlung des Plattenepithelcarcinoms der Speiseröhre. Internist 31:131, 1994

    Google Scholar 

  2. Roder, J.D., Busch, R., Stein, H.J., Fink, U., Siewert, J.R.: Ratio of invaded to removed lymph nodes as a predictor of survival in squamous cell carcinoma of the esophagus. Br. J. Surg. 81:410, 1993

    Article  Google Scholar 

  3. Burkhardt, R., Frisch, B., Kettner, G.: The clinical study of micrometastic cancer by bone biopsy. Bull. Cancer (Paris) 67:291, 1980

    CAS  Google Scholar 

  4. Mansi, J.L., Berger, U., Easton, D., et al.: Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases. B.M.J. 295:1093, 1987

    Article  CAS  Google Scholar 

  5. Cohen, Y., Gershoni-Baruch, R., Lichtic, C.: Bone marrow biopsy in patients with malignant neoplasms other than lymphomas or leukemia. Acta Haematol. 62:181, 1979

    Article  CAS  PubMed  Google Scholar 

  6. Fidler, I.J.: Metastasis: quantitative analysis of distribution and fate of tumor emboli labeled with 125I-5-iodo-2-deoxyuridine. J. Natl. Cancer Inst. 45:773, 1970

    CAS  PubMed  Google Scholar 

  7. Gurmukh, S., Krause, J.R., Breitfeld, V.: Bone marrow examination for metastatic tumor. Cancer 40:2317, 1977

    Article  Google Scholar 

  8. Schlimok, G., Funke, I., Holtzmann, B., et al.: Micrometastic 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. 84:8672, 1987

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Cote, R., Rosen, P., Old, L., Osborne, M.: Detection of bone marrow micrometastasis in patients with early-stage breast cancer. Diagn. Oncol. 1:37, 1987

    Google Scholar 

  10. Dearnaley, D.P., Sloane, J.P., Omerod, M.G., et al.: Increased detection of mammary carcinoma cells in marrow smears using antisera to epithelial membrane antigen. Br. J. Cancer 44:85, 1984

    Article  Google Scholar 

  11. Lindemann, F., Schlimok, G., Dischedl, P., Witte, J., Riethmüller, G.: Prognostic significance of micrometastic tumour cells in bone marrow of colorectal cancer cells. Lancet 340:685, 1992

    Article  CAS  PubMed  Google Scholar 

  12. Moss, T.J., Reynolds, C.P., Harland, P.D., et al.: Prognostic value of immunocytologic detection of bone marrow metastases in neuroblastoma. N. Engl. J. Med. 324:219, 1991

    Article  CAS  PubMed  Google Scholar 

  13. Pantel, K., Izbicki, J.R., Angstwurm, M., et al.: Immunocytological detection of bone marrow micrometastasis in operable non-small cell lung cancer. Cancer Res. 53:1027, 1993

    CAS  PubMed  Google Scholar 

  14. Schlimok, G., Funke, I., Pantel, K., et al.: Micrometastic tumour cells in bone marrow of patients with gastric cancer: methodological aspects of detection and prognostic significance. Eur. J. Cancer 27:1461, 1991

    Article  CAS  PubMed  Google Scholar 

  15. Hermanek, P., Scheibe, O., Spiessl, B., Wagner, G.: TNM-Klassifikation maligner Tumoren. Berlin, Springer-Verlag 1993, p. 102

    Google Scholar 

  16. Debus, E., Weber, K., Osborne, M.: Monoclonal cytokeratin antibodies that distinguish simple from stratified squamous epithelia. EMBO J. 1:1641, 1982

    CAS  PubMed  Google Scholar 

  17. Viac, J., Reano, J., Brochier, J., Staquet, M., Thivolet, J.: Reactivity pattern of monoclonal anti-keratin antibody (KL1). J. Invest. Dermatol. 81:351, 1983

    Article  CAS  PubMed  Google Scholar 

  18. Karsten, U., Papsdorf, G., Roloff, G.: Monoclonal anticytokeratin antibody from a hybridoma clone generated by electrofusion. Eur. J. Cancer Clin. Oncol. 21:735, 1985

    Google Scholar 

  19. Kasper, M., Stosiek, P., Typlt, H., et al.: Histological evaluation of three new monoclonal anti-cytokeratin a antibodies. I. Normal tissues. Eur. J. Cancer Clin. Oncol. 23:137, 1987

    Article  CAS  PubMed  Google Scholar 

  20. Cordell, J.L., Falini, B., Erber, W.N., et al.: Immunozymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J. Histochem. Cytochem. 32:219, 1984

    Article  CAS  PubMed  Google Scholar 

  21. Diel, I.J., Kaufmann, M., Goemer, R.S., Costa, D., Kaul, S., Bestest, G.: Detection of tumor cells in bone marrow of patients with breast and colorectal cancer: a prognostic factor for distant metastasis. J. Clin. Oncol. 10:1534, 1992

    CAS  PubMed  Google Scholar 

  22. Harrison, W.J.: The total cellularity of the bone marrow in man. J. Clin. Pathol. 15:254, 1962

    Article  CAS  PubMed  Google Scholar 

  23. Riethmüller, G., Johnson, J.P.: Monoclonal antibodies in the detection and therapy of micrometastatic epithelial cancers. Curr. Opin. Immunol. 4:647, 1992

    Article  PubMed  Google Scholar 

  24. Pantel, K., Schlimok, G., Angstwurm, M., et al.: Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow. J. Hematother. 3:165, 1994

    Article  CAS  PubMed  Google Scholar 

  25. Schwarz, G.: Cytomorphology and cell yield in a new cytocentrifugal technique allowing collection of the cell-free supernatant. Lab. Med. 15:45, 1991

    Google Scholar 

  26. Paget, S.: The distribution of secondary growth in cancer of the breast. Lancet 1:571, 1889

    Article  Google Scholar 

  27. Anderson, L.L., Lad, T.E.: Autopsy findings in squamous-cell carcinoma of the esophagus. Cancer 50:1587, 1982

    Article  CAS  PubMed  Google Scholar 

  28. Mandard, A.M., Chasle, J., Marnay, J., et al.: Autopsy findings in 111 cases of esophageal cancer. Cancer 48:329, 1981

    Article  CAS  PubMed  Google Scholar 

  29. Bosch, A., Frias, Z., Caldwell, W.L., Jaeschke, W.H.: Autopsy findings in carcinoma of the esophagus. Acta Radiol. Oncol. 18:103, 1979

    Article  CAS  Google Scholar 

  30. Schoenfeld, A., Luqmani, Y., Smith, D., et al.: Detection of breast micrometastases in axillary lymph nodes by using polymerase chain reaction. Cancer Res. 54:2986, 1994

    CAS  PubMed  Google Scholar 

  31. Datta, Y.H., Adams, P.T., Drobyski, W.R., Ethler, S.P., Terry, V.H., Roth, M.S.: Sensitive detection of occult breast cancer by the reversetranscriptase polymerase chain reaction. J. Clin. Oncol. 12:475, 1994

    CAS  PubMed  Google Scholar 

  32. Traweek, S., Liu, J., Battifora, H.: Keratin gene expression in non epithelial tissues: detection with polymerase chain reaction. Am. J. Pathol. 142:1111, 1993

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Technical University of Munich, Ismaningerstrasse 22, 81675, Munich, Germany

    Stefan Thorban M.D., Jürgen D. Roder M.D., Hjalmar Nekarda M.D. & J. Rüdiger Siewert FACS

  2. Institute of Pathology and Pathologic Anatomy, Technical University of Munich, Trogerstrasse 7, 81675, Munich, Germany

    Armin Funk M.D.

  3. Institute of Immunology, Ludwig-Maximilians University, Goethestrasse 31, 80336, Munich, Germany

    Klaus Pantel M.D.

Authors
  1. Stefan Thorban M.D.
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  2. Jürgen D. Roder M.D.
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  3. Hjalmar Nekarda M.D.
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  4. Armin Funk M.D.
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  5. Klaus Pantel M.D.
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  6. J. Rüdiger Siewert FACS
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Thorban, S., Roder, J.D., Nekarda, H. et al. Disseminated Epithelial Tumor Cells in Bone Marrow of Patients with Esophageal Cancer: Detection and Prognostic Significance. World J. Surg. 20, 567–573 (1996). https://doi.org/10.1007/s002689900088

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