Immunohistochemical analysis of primary breast tumors and tumor-draining lymph nodes by means of the T-cell costimulatory molecule OX-40.
OBJECTIVE
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.
Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, Portland, Oregon 97213, USA.
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Ramstad
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Lawnicki
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Vetto
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Weinberg
D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D007167:Immunotherapy / Q000379:methods; D008207:Lymphatic Metastasis / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D015203:Reproducibility of Results; D012189:Retrospective Studies; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis* / Q000502:physiology
D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7