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Correlation of Tissue and Plasma RANTES Levels with Disease Course in Patients with Breast or Cervical Cancer

Niwa Institute for Immunology, Tosashimizu 787-0303 [Y. N., H. S.]; Department of Dermatology, Kansai Medical University, Moriguchi 570-8507 [H. A.]; Gynecological Department, Hyogo Prefectural Amagasaki Hospital, Amagasaki 660-0828 [H. N.]; Department of Clinical and Laboratory Medicine, Yamanashi Medical University, Yamanashi 409-3898 [Y. O.]; and Research and Development, Sumitomo Metal Bio-Science, Inc., Sagamihara 229-0004 [A. A.], Japan

The ß-chemokine RANTES was measured in plasma in 43 patients with breast cancer and in 23 patients with cervical cancer, and the RANTES content in primary tumors, tumor metastatic to lymph nodes, and clinically normal skin or pelvic mucosa was measured. In addition, plasma levels were determined in all of the patients for the platelet-derived chemokine ß-thromboglobulin (ß-TG) and for IFN-, interleukin (IL)-2, IL-4, IL-5, and IL-10, along with serum IgE levels and blood eosinophils. Plasma RANTES levels were found to be higher in order of stages IV, III, II, and I of each cancer except for stage I. A marked increase in plasma RANTES level (>10,000 pg/ml) was found in 27% of patients with progressive malignancy but in none of those in clinical remission. The platelet RANTES content was correspondingly decreased in those patients with increased plasma RANTES levels. ß-TG showed a pattern similar to RANTES both in plasma and platelets, but with much less dramatic differences between patients with different stages of disease. Other allergic parameters, IgE, eosinophils and plasma IFN-, IL-2, -5, and -10, were not elevated in the cancer patients. The RANTES content was markedly elevated in the primary tumor and metastatic lesions (lymph node or skin) from all of the patients with breast or cervical cancer, irrespective of the plasma RANTES level. In addition, in patients with progressive breast or cervical cancer, but not in patients thought to be cured of these tumors, the RANTES content was markedly increased in clinically normal tissue taken from near the operative site several months postoperatively, as well as in intact skin or mucosa taken perioperatively near the excised tumor. This study suggests an as-yet-undefined but important role played by RANTES in carcinogenesis, as well as the possibility that a RANTES assay in tissue surrounding a tumor or postoperative tumor site may help predict prognosis in these patients.

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