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

Trygg Ramstad, Lyle Lawnicki, John Vetto, Andrew Weinberg

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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. (C) 2000 by Excerpta Medica, Inc.

Original languageEnglish (US)
Pages (from-to)400-406
Number of pages7
JournalAmerican journal of surgery
Issue number5
StatePublished - May 15 2000

ASJC Scopus subject areas

  • Surgery


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