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Published in: Cellular Oncology 5/2013

01-10-2013 | Original Paper

FOXP3 expression and nodal metastasis of breast cancer

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

Published in: Cellular Oncology | Issue 5/2013

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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.
Literature
1.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
2.
go back to reference J.I. Ellyard, L. Simson, C.R. Parish, Th2-mediated anti-tumour immunity: friend or foe? Tissue Antigens 70, 1–11 (2007)PubMedCrossRef J.I. Ellyard, L. Simson, C.R. Parish, Th2-mediated anti-tumour immunity: friend or foe? Tissue Antigens 70, 1–11 (2007)PubMedCrossRef
3.
go back to reference H. Murakami, H. Ogawara, H. Hiroshi, Th1/Th2 cells in patients with multiple myeloma. Hematology 9, 41–45 (2004)PubMedCrossRef H. Murakami, H. Ogawara, H. Hiroshi, Th1/Th2 cells in patients with multiple myeloma. Hematology 9, 41–45 (2004)PubMedCrossRef
4.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
5.
go back to reference R.M. Lopez, M. Moser, Dendritic cell subsets and the regulation of Th1/Th2 responses. Sem. Immunol. 13, 275–282 (2001)CrossRef R.M. Lopez, M. Moser, Dendritic cell subsets and the regulation of Th1/Th2 responses. Sem. Immunol. 13, 275–282 (2001)CrossRef
6.
go back to reference R.B. Effros, Replicative senescence of CD8 T cells: potential effects on cancer immune surveillance and immunotherapy. Cancer Immunol. Immunother. 53, 925–933 (2004)PubMedCrossRef R.B. Effros, Replicative senescence of CD8 T cells: potential effects on cancer immune surveillance and immunotherapy. Cancer Immunol. Immunother. 53, 925–933 (2004)PubMedCrossRef
7.
go back to reference Z. Fehervari, S. Sakaguchi, CD4+ Tregs and immune control. J. Clin. Invest. 114, 1209–1217 (2004)PubMed Z. Fehervari, S. Sakaguchi, CD4+ Tregs and immune control. J. Clin. Invest. 114, 1209–1217 (2004)PubMed
9.
go back to reference S. Hori, T. Nomura, S. Sakaguchi, Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057–1061 (2003)PubMedCrossRef S. Hori, T. Nomura, S. Sakaguchi, Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057–1061 (2003)PubMedCrossRef
10.
go back to reference 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 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
11.
go back to reference 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 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
12.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
13.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
14.
go back to reference S. Sakaguchi, The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery. J. Clin. Invest. 112, 1310–1312 (2003)PubMed S. Sakaguchi, The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery. J. Clin. Invest. 112, 1310–1312 (2003)PubMed
15.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
16.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
17.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
18.
go back to reference E.G. Mansour, P.M. Ravdin, L. Dressler, Prognostic factors in early breast carcinoma. Cancer 74, 381–400 (1994)PubMedCrossRef E.G. Mansour, P.M. Ravdin, L. Dressler, Prognostic factors in early breast carcinoma. Cancer 74, 381–400 (1994)PubMedCrossRef
19.
go back to reference 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 398–401PubMedCrossRef 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 398–401PubMedCrossRef
20.
go back to reference 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 340PubMedCrossRef 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 340PubMedCrossRef
21.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
22.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
23.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
24.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
25.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
26.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
27.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
28.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
29.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
30.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
Metadata
Title
FOXP3 expression and nodal metastasis of breast cancer
Authors
Yesim Gökmen-Polar
Mangesh A. Thorat
Payal Sojitra
Rashmil Saxena
Sunil Badve
Publication date
01-10-2013
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 5/2013
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-013-0147-3

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