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Immunophenotype of lymphocytic infiltration in medullary carcinoma of the breast

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Abstract

Medullary carcinoma (MC) of the breast is characterized by large anaplastic cells and infiltration by benign lymphocytes. Patients with this pattern of breast carcinoma are considered to have a better prognosis than those with other histological subtypes. We reviewed cases of primary breast carcinoma that were surgically resected between 1990 and 2004. Of these, 13 cases of medullary carcinoma of the breast with lymphocyte infiltration were reported. Tests for CD3, CD4, CD8, CD20, CD56, TIA-1, and granzyme B were performed on paraffin sections. We found that the MC contained very few NK cells, as assessed by their reactivity with the CD56 antibodies. However, MC had a significantly greater percentage of CD3, CD8, TIA-1, and granzyme B lymphocytes infiltrating the stroma of the tumor. Furthermore, more CD8-positive than CD4-positive T-cell lymphocytes were present within the tumor cell nests in MC, as opposed to the proportion in usual ductal carcinoma. The infiltrating cytotoxic/suppressor T cells in MC represent host resistance against cancer, and the high grading of the T-cell infiltration could explain, in part, a key mechanism controlling the good prognosis for this type of tumor and solve the pathological paradox of MC.

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References

  1. Arlen M, Flores L, Elguezbal A, Levowitz BS (1976) Nodal response in medullary carcinoma of the breast. Am J Surg 131:263–266

    Article  CAS  PubMed  Google Scholar 

  2. Ben-Ezra J, Sheibani K (1987) Antigenic phenotype of the lymphocytic component of medullary carcinoma of the breast. Cancer 59:2037–2041

    CAS  PubMed  Google Scholar 

  3. Bhan AK, DesMarais CL (1983) Immunohistologic characterization of major histocompatibility antigens and inflammatory cellular infiltrate in human breast cancer. J Natl Cancer Inst 71:507–516

    CAS  PubMed  Google Scholar 

  4. Bloom HJG, Richardson WW, Filed JR (1970) Host resistance and survival in carcinoma of the breast a study of 104 cases of medullary carcinoma is a series of 1,411 cases of breast cancer followed for 20 years. BMJ 3:181–187

    CAS  PubMed  Google Scholar 

  5. Gaffey MJ, Frierson HF, Mills SE, Boyd JC, Zarbo RI, Simpson JF, Gross LK, Weiss LM (1993) Medullary carcinoma of the breast. Identification of lymphocyte subpopulations and their significance. Mod Pathol 6:721–728

    CAS  PubMed  Google Scholar 

  6. Gaudin C, Dietrich PY, Robache S, Guillard M, Escudier B, Lacombe MJ, Kumar A, Triebel F, Caignard A (1995) In vivo local expansion of clonal T cell subpopulations in renal cell carcinoma. Cancer Res 55:685–690

    CAS  PubMed  Google Scholar 

  7. Georgiannos SN, Renaut A, Goode AW, Sheaff M (2003) The immunophenotype and activation status of the lymphocytic infiltrate in human breast cancers, the role of the major histocompatibility complex in cell-mediated immune mechanisms, and their association with prognostic indicators. Surgery 134:827–834

    Article  PubMed  Google Scholar 

  8. Hudson JM, Castilleja A, Murray JL, Honda T, Kudelka A, Singletary E, Wharton JT, Ioannides CG (1998) Growth and antigen recognition of tumor-infiltrating lymphocytes from human breast cancer. J Interferon Cytokine Res 18:529–536

    CAS  PubMed  Google Scholar 

  9. Marrogi AJ, Munshi A, Merogi AJ, Ohadike Y, El-Habashi A, Marrogi OL, Freeman SM (1997) Study of tumor infiltrating lymphocytes and transforming growth factor-beta as prognostic factors in breast carcinoma. Int J Cancer 74:492–501

    Article  CAS  PubMed  Google Scholar 

  10. Moore OS, Foote FW (1949) The relatively favorable prognosis of medullary carcinomas of the breast. Cancer 2:635–642

    Google Scholar 

  11. O’Mahony AM, O’Sullivan GC, O’Connell J, Cotter TG, Collins JK (1993) An immune suppressive factor derived from esophageal squamous carcinoma induces apoptosis in normal and transformed cells of lymphoid lineage. J Immunol 151:4847–4856

    PubMed  Google Scholar 

  12. Rapin V, Contesso G, Mouriesse H, Bertin F, Lacombe MJ, Piekarski JD, Travagli JP, Gadenne C, Friedman S (1988) Medullary breast carcinoma: a reevaluation of 95 cases of breast cancer with inflammatory stroma. Cancer 19:2503–2510

    Google Scholar 

  13. Reinfuss M, Stelmach A, Mitus J, Rys J, Duda K (1995) Typical medullary carcinoma of the breast: a clinical and pathological analysis of 52 cases. J Surg Oncol 60:89–94

    CAS  PubMed  Google Scholar 

  14. Restifo NP, Marincola FM, Kawakami Y, Taubenberger J, Yannelli JR, Rosenberg SA (1996) Loss of functional beta 2-microglobulin in metastatic melanomas from five patients receiving immunotherapy. J Natl Cancer Inst 88:100–108

    CAS  PubMed  Google Scholar 

  15. Ridolfi RL, Rosen PP, Port A, Kinne D, Mike V (1977) Medullary carcinoma of the breast: a clinicopathologic study with 10-year follow up. Cancer 40:1365–1385

    CAS  PubMed  Google Scholar 

  16. Shimokawara I, Imamura M, Yamakawa N, Ishii Y, Kikuchi K (1982) Identification of lymphocyte subpopulations in human breast cancer tissue and its significance: an immunoperoxidase study with anti-human T-and B-cell sera. Cancer 49:1456–1464

    CAS  PubMed  Google Scholar 

  17. Tanaka H, Hori M, Ohki T (1992) High endothelial venule and immunocomponent cells in typical medullary carcinoma of the breast. Virchows Arch 420:253–261

    CAS  Google Scholar 

  18. Tamiolakis D, Simopoulos C, Cheva A, Lambropoulou M, Kotini A, Jivannakis T, Papadopoulos N (2002) Immunophenotypic profile of tumor infiltrating lymphocytes in medullary carcinoma of the breast. Eur J Gynaec Oncol 23:433–436

    CAS  Google Scholar 

  19. Toso JF, Oei C, Oshidari F, Tartaglia J, Paoletti E, Lyerly HK, Talib S, Weinhold KJ (1996) MAGE-1-specific precursor cytotoxic T-lymphocytes present among tumor-infiltrating lymphocytes from a patient with breast cancer: characterization and antigen-specific activation. Cancer Res 56:16–20

    CAS  PubMed  Google Scholar 

  20. Wargotz ES, Silverberg SG (1988) Medullary carcinoma of the breast: a clinicopathologic study with appraisal of current diagnostic criteria. Hum Pathol 19:1340–1346

    CAS  PubMed  Google Scholar 

  21. Yakirevich E, Izhak OB, Rennert G, Kovacs ZG, Resnick MB (1999) Cytotoxic phenotype of tumor infiltrating lymphocytes in medullary carcinoma of the breast. Mod Pathol 12:1050–1056

    CAS  PubMed  Google Scholar 

  22. Yazawa T, Kamma H, Ogata T (1993) Frequent expression of HLA-DR antigen in medullary carcinoma of the breast. A possible reason for its prominent lymphocytic infiltration and favorable prognosis. Appl Immunohistochem 1:289–296

    Google Scholar 

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Acknowledgements

We sincerely thank A. Adachi, M.D., I. Miura, M.D., Y. Toyosumi, M.D., S. Momose, M.D., T. Ougida, C.T., M. Abe, C.T., T. Saito, C.T., K. Kiuchi, C.T., K. Ohsawa, C.T., K. Matsuno, C.T., K. Hanami, C.T., Y. Ohno, C.T. and T. Masuda, C.T. for their technical assistance and advice.

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Correspondence to Hajime Kuroda.

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Kuroda, H., Tamaru, Ji., Sakamoto, G. et al. Immunophenotype of lymphocytic infiltration in medullary carcinoma of the breast. Virchows Arch 446, 10–14 (2005). https://doi.org/10.1007/s00428-004-1143-9

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