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FOXP3 expression and nodal metastasis of breast cancer

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Abstract

Purpose

T regulatory cells, a subset of T lymphocytes, function to suppress immune responses. FOXP3, a member of the forkhead family of transcription factors, is a good marker for T regulatory cells. Since sentinel nodes are important sites of immunomodulation in breast cancer, we studied the association between T regulatory cells and nodal metastasis using FOXP3 expression in sentinel nodes with and without metastatic breast carcinoma.

Methods

Following sample size calculations, we selected 140 sentinel nodes from breast cancer patients; 70 with metastasis (sentinel node+) and 70 without metastasis (sentinel node–). FOXP3 expression in sentinel nodes was studied by immunohistochemistry. Cortical cells expressing FOXP3 were counted in 10 high power fields.

Results

In the evaluable cases, the node positive (n = 66) and negative (n = 69) groups were well balanced for all clinicopathological parameters except histological type. The mean number of T regulatory cells expressing FOXP3 (per 10 hpf) was 139 in the node positive and 132 in the node negative group (P = 0.540). The mean number of T regulatory cells was 162 in patients ≤35 years of age (n = 8) compared to 133 in older patients (P = 0.250). Primary tumor pathological characteristics like tumor type, grade, size, and ER, PR, and HER2 status did not correlate with FOXP3 expression.

Conclusions

The number of FOXP3-expressing T regulatory cells does not differ significantly between sentinel node+ and sentinel node– samples. It was also not affected by primary tumor characteristics like tumor type, grade, size, hormone receptor, and HER2 status.

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References

  1. T.R. Mosmann, R.L. Coffman, TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 7, 145–173 (1989)

    Article  PubMed  CAS  Google Scholar 

  2. J.I. Ellyard, L. Simson, C.R. Parish, Th2-mediated anti-tumour immunity: friend or foe? Tissue Antigens 70, 1–11 (2007)

    Article  PubMed  CAS  Google Scholar 

  3. H. Murakami, H. Ogawara, H. Hiroshi, Th1/Th2 cells in patients with multiple myeloma. Hematology 9, 41–45 (2004)

    Article  PubMed  CAS  Google Scholar 

  4. A.M. Thornton, E.M. Shevach, CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 188, 287–296 (1998)

    Article  PubMed  CAS  Google Scholar 

  5. R.M. Lopez, M. Moser, Dendritic cell subsets and the regulation of Th1/Th2 responses. Sem. Immunol. 13, 275–282 (2001)

    Article  Google Scholar 

  6. R.B. Effros, Replicative senescence of CD8 T cells: potential effects on cancer immune surveillance and immunotherapy. Cancer Immunol. Immunother. 53, 925–933 (2004)

    Article  PubMed  Google Scholar 

  7. Z. Fehervari, S. Sakaguchi, CD4+ Tregs and immune control. J. Clin. Invest. 114, 1209–1217 (2004)

    PubMed  CAS  Google Scholar 

  8. M. Dougan, G. Dranoff, Immune therapy for cancer. Annu. Rev. Immunol. 27, 83–117 (2009)

    Article  PubMed  CAS  Google Scholar 

  9. S. Hori, T. Nomura, S. Sakaguchi, Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057–1061 (2003)

    Article  PubMed  CAS  Google Scholar 

  10. B.K. Halak, H.C. Maguire Jr., E.C. Lattime, Tumor-induced interleukin-10 inhibits type 1 immune responses directed at a tumor antigen as well as a non-tumor antigen present at the tumor site. Cancer Res. 59, 911–917 (1999)

    PubMed  CAS  Google Scholar 

  11. F. Ichihara, K. Kono, A. Takahashi, H. Kawaida, H. Sugai, H. Fujii, Increased populations of regulatory T cells in peripheral blood and tumor-infiltrating lymphocytes in patients with gastric and esophageal cancers. Clin. Cancer Res. 9, 4404–4408 (2003)

    PubMed  Google Scholar 

  12. C. Rieser, R. Ramoner, L. Holtl, H. Rogatsch, C. Papesh, A. Stenzl, G. Bartsch, M. Thurnher, Mature dendritic cells induce T-helper type-1-dominant immune responses in patients with metastatic renal cell carcinoma. Urol. Int. 63, 151–159 (1999)

    Article  PubMed  CAS  Google Scholar 

  13. J.D. Fontenot, M.A. Gavin, A.Y. Rudensky, Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4, 330–336 (2003)

    Article  PubMed  CAS  Google Scholar 

  14. S. Sakaguchi, The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery. J. Clin. Invest. 112, 1310–1312 (2003)

    PubMed  CAS  Google Scholar 

  15. M. Gobert, I. Treilleux, N. Bendriss-Vermare, T. Bachelot, S. Goddard-Leon, V. Arfi, C. Biota, A.C. Doffin, I. Durand, D. Olive, S. Perez, N. Pasqual, C. Faure, I. Ray-Coquard, A. Puisieux, C. Caux, J.-Y. Blay, C. Ménétrier-Caux, Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. Cancer Res. 69, 2000–2009 (2009)

    Article  PubMed  CAS  Google Scholar 

  16. A. Merlo, P. Casalini, M.L. Carcangiu, C. Malventano, T. Triulzi, S. Mènard, E. Tagliabue, A. Balsari, FOXP3 expression and overall survival in breast cancer. J. Clin. Oncol. 27, 1746–1752 (2009)

    Article  PubMed  CAS  Google Scholar 

  17. M. Ohara, Y. Yamaguchi, K. Matsuura, S. Murakami, K. Arihiro, M. Okada, Possible involvement of regulatory T cells in tumor onset and progression in primary breast cancer. Cancer Immunol. Immunother. 58, 441–447 (2009)

    Article  PubMed  CAS  Google Scholar 

  18. E.G. Mansour, P.M. Ravdin, L. Dressler, Prognostic factors in early breast carcinoma. Cancer 74, 381–400 (1994)

    Article  PubMed  CAS  Google Scholar 

  19. A.E. Giuliano, D.M. Kirgan, J.M. Guenther, D.L. Morton, Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann. Surg. 220, 391–398 (1994). discussion 398–401

    Article  PubMed  CAS  Google Scholar 

  20. D.N. Krag, D.L. Weaver, J.C. Alex, J.T. Fairbank, Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg. Oncol. 2, 335–339 (1993). discussion 340

    Article  PubMed  CAS  Google Scholar 

  21. D.L. Morton, D.R. Wen, J.H. Wong, J.S. Economou, L.A. Cagle, F.K. Storm, L.J. Foshag, A.J. Cochran, Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch. Surg. 127, 392–399 (1992)

    Article  PubMed  CAS  Google Scholar 

  22. N.J. Poindexter, A. Sahin, K.K. Hunt, E.A. Grimm, Analysis of dendritic cells in tumor-free and tumor-containing sentinel lymph nodes from patients with breast cancer. Breast Cancer Res. 6, R408–R415 (2004)

    Article  PubMed  CAS  Google Scholar 

  23. R.R. Huang, D.-R. Wen, J. Guo, A.E. Giuliano, M. Nguyen, R. Offodile, S. Stern, R. Turner, A.J. Cochran, Selective modulation of paracortical dendritic cells and T-lymphocytes in breast cancer sentinel lymph nodes. Breast J. 6, 225–232 (2000)

    Article  PubMed  Google Scholar 

  24. S. Ishigami, S. Natsugoe, Y. Uenosono, Y. Hata, A. Nakajo, F. Miyazono, M. Matsumoto, S. Hokita, T. Aikou, Infiltration of antitumor immunocytes into the sentinel node in gastric cancer. J. Gastrointest. Surg. 7, 735–739 (2003)

    Article  PubMed  Google Scholar 

  25. J. Schule, L. Bergkvist, L. Hakansson, B. Gustafsson, A. Hakansson, Down-regulation of the CD3-zeta chain in sentinel node biopsies from breast cancer patients. Breast Cancer Res. Treat. 74, 33–40 (2002)

    Article  PubMed  Google Scholar 

  26. K. Matsuura, Y. Yamaguchi, H. Ueno, A. Osaki, K. Arihiro, T. Toge, Maturation of dendritic cells and T-cell responses in sentinel lymph nodes from patients with breast carcinoma. Cancer 106, 1227–1236 (2006)

    Article  PubMed  CAS  Google Scholar 

  27. A.S. Mansfield, P.S. Heikkila, A.T. Vaara, K.A. von Smitten, J.M. Vakkila, M.H. Leidenius, Simultaneous Foxp3 and IDO expression is associated with sentinel lymph node metastases in breast cancer. BMC Cancer 9, 231 (2009)

    Article  PubMed  Google Scholar 

  28. K. Matsuura, Y. Yamaguchi, A. Osaki, M. Ohara, R. Okita, A. Emi, S. Murakami, K. Arihiro, FOXP3 expression of micrometastasis-positive sentinel nodes in breast cancer patients. Oncol. Rep. 22, 1181–1187 (2009)

    Article  PubMed  CAS  Google Scholar 

  29. R. Nakamura, M. Sakakibara, T. Nagashima, T. Sangai, M. Arai, T. Fujimori, S. Takano, T. Shida, Y. Nakatani, M. Miyazaki et al., Accumulation of regulatory T cells in sentinel lymph nodes is a prognostic predictor in patients with node-negative breast cancer. Eur. J. Cancer 45, 2123–2131 (2009)

    Article  PubMed  CAS  Google Scholar 

  30. S.P.L. Leong, M. Peng, Y.M. Zhou, J.E. Vaquerano, J.W.C. Chang, Cytokine profiles of sentinel lymph nodes draining the primary melanoma. Ann. Surg. Oncol. 9, 82–87 (2002)

    Article  PubMed  Google Scholar 

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Acknowledgements

SB is supported by Susan B Komen Scholar Grant.

Conflict of interests

None.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, IU School of Medicine, Indianapolis, IN, 46202, USA

    Yesim Gökmen-Polar, Mangesh A. Thorat, Payal Sojitra, Rashmil Saxena & Sunil Badve

  2. Department of Internal Medicine, IU School of Medicine, Indianapolis, IN, 46202, USA

    Sunil Badve

  3. Department of Pathology, Indiana University School of Medicine, 635 Barnhill Drive, MS-A128, Indianapolis, IN, 46202, USA

    Sunil Badve

Authors
  1. Yesim Gökmen-Polar
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  2. Mangesh A. Thorat
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  3. Payal Sojitra
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  5. Sunil Badve
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Correspondence to Sunil Badve.

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Gökmen-Polar, Y., Thorat, M.A., Sojitra, P. et al. FOXP3 expression and nodal metastasis of breast cancer. Cell Oncol. 36, 405–409 (2013). https://doi.org/10.1007/s13402-013-0147-3

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  • DOI: https://doi.org/10.1007/s13402-013-0147-3

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