title: [Tumor infiltrating regulatory T cells in human breast cancer and associated draining lymph nodes: an in-situ analysis].
abstract: OBJECTIVE
  To retrospectively analyze the quantity and status of the tumor infiltrating regulatory T lymphocytes in breast cancer and the draining lymph nodes, and to elucidate the clinical pathologic significance.
  
  
  METHODS
  Seventy-four breast cancer samples with excised axillary lymph nodes were typed and staged histopathologically. The regulatory T lymphocytes were labeled by immunohistochemistry using EnVision method with the monoclonal antibodies against CD25 and Foxp3, and the immunophenotype was analyzed. In addition, the expression of IFN-γ, IL-10 and TGF-β1 mRNA in lymphocytes of lymph nodes draining the tumors was detected by in situ hybridization with the corresponding specific oligo nucleaic acid probes.
  
  
  RESULTS
  The number of CD25(+)Foxp3(+) T cells infiltrating the interstitium was much higher than that in the parenchymal tissue of the cancer. In the tumor draining lymph nodes, CD25(+) cells and Foxp3(+) cells were predominantly distributed in the paracortex with a proliferative pattern. TGF-β1, INF-γ and IL-10 mRNA positive cells showed a similar distribution pattern in the draining lymph nodes. Among the 39 cases with metastatic disease, the lymph nodes with metastases showed a much higher number of CD25(+)Foxp3(+) cells than that without metastases (23.5 vs 17.3 and 23.8 vs 15.5; P < 0.05). However, there was no difference in the density of Foxp3(+)CD25(+) cells in the draining lymph nodes between the death and survival groups (P > 0.05). Cytokine expression of TGF-β1, IL-10 and IFN-γ mRNA in the lymphocytes of draining lymph nodes in 24 cases showed that there were more IL-10 mRNA positive cells in the dead patients than that in the survived patients. A similar trend was observed for TGF-β1 mRNA positive cells but the difference was not statistically significant (P > 0.05). The expression rate of TGF-β1 and IL-10 mRNA in the draining lymph nodes was proportional to that of CD25(+) and Foxp3(+) cells (P < 0.05), and the expression of TGF-β1 positive cells was also proportional to that of IL-10 mRNA positive cells (P < 0.01). The expression of IFN-γ mRNA among these groups showed no significance (P > 0.05).
  
  
  CONCLUSIONS
  Regulatory T cells may play important roles in inhibiting the host antitumor immunity, and the presence of increased regulatory T cells and Th2-secreting cells in paracortex with a proliferative pattern in the tumor draining lymph nodes implies that the paracortical proliferation of draining lymph nodes may not reflect positive antitumor effects.
authors.affiliation: Xi'an Jiaotong University, Xi'an, China.
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Wang
authors.forename: Qin-feng
authors.initials: QF
authors.lastname: Shi
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Jian-jun
authors.initials: JJ
authors.lastname: He
authors.forename: Yi-li
authors.initials: YL
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D007371:Interferon-gamma