Immunohistochemical analysis of primary breast tumors and tumor-draining lymph nodes by means of the T-cell costimulatory molecule OX-40

Am J Surg. 2000 May;179(5):400-6. doi: 10.1016/s0002-9610(00)00361-5.

Abstract

Objectives: The OX-40 receptor (OX-40R/CD134) is expressed primarily on activated CD4(+) ("helper") T cells. We have previously reported the presence of OX-40(+) T cells in head and neck cancer and melanoma, where they appear to be restricted to tumor compartments (primary tumor infiltrating lymphocytes [TILs] and draining lymph node cells) and therefore may represent the tumor antigen-specific CD4(+) T cells.

Methods: In order to determine the degree of OX-40R expression, and any relationship with the presence of tumor cells (lobular and/or infiltrating ductal carcinoma), 45 archived paraffin-embedded breast primary tumors and their associated draining (axillary) lymph nodes were retrospectively analyzed using standard immunohistochemical techniques.

Results: Seven of 45 primary tumors (16%) and 7 of 29 with lympocytic infiltrates (24%) were noted to have elevated levels of OX-40R(+) lymphocytes within the tumor specimens, including 2 of 4 specimens thought to have only "pure" ductal carcinoma in situ (DCIS). No OX-40R(+) lymphocytes were noted in normal breast tissue. Twenty-one (43%) patients had axillary metastases at the time of resection. High levels of OX-40R expression was seen in 9 (45%) of these 21 axillary node specimens, whereas no such staining was seen in the node-negative specimens (P <0.001). Furthermore, in a patient thought to be without axillary disease, several subcapsular single-cell metastases were retrospectively discovered near a lone cluster of OX-40R(+) lymphocytes. In general, visual inspection showed OX-40R(+) T cells to be in close proximity to tumor and often in direct contact with metastatic cells.

Conclusions: The OX-40R is upregulated on lymphocytes within tumor draining lymph nodes, and these lymphocytes are specifically localized around tumor deposits. These data imply that OX-40R immunostaining may be useful for both determination of occult involvement of lymph nodes by tumor and for identification of potential candidates for future OX-40 based immunotherapy.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, MHC Class II / genetics
  • Genes, MHC Class II / immunology
  • Humans
  • Immunohistochemistry / methods*
  • Immunotherapy / methods
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / immunology
  • Lymphatic Metastasis / pathology*
  • Middle Aged
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor*
  • Reproducibility of Results
  • Retrospective Studies
  • T-Lymphocytes, Helper-Inducer / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / analysis*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / physiology

Substances

  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • TNFRSF4 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 7