Elevated serum RANTES levels in patients with ovarian cancer correlate with the extent of the disorder

doi:10.1016/j.ygyno.2006.01.029

Gynecologic Oncology

Volume 102, Issue 3, September 2006, Pages 542-545

https://doi.org/10.1016/j.ygyno.2006.01.029 Get rights and content

Abstract

Objective.

To assess the clinical relevance of serum regulated upon activation, normal T-cell expressed and secreted (RANTES) levels in distinguishing patients with ovarian cancers from those with benign ovarian cysts, we measured its concentration with reference to the disease stage, pathological grading, histological subtype, and the residual tumor mass.

Methods.

Preoperative serum RANTES levels were measured in women with invasive epithelial ovarian cancer (n = 52), borderline ovarian tumor (n = 6), benign ovarian cysts (n = 28), or normal controls (n = 12) using an enzyme-linked immunosorbent assay.

Results.

The serum RANTES concentration was significantly elevated in the ovarian cancer patients (median 53 ng/ml, interquartile range 23–104 ng/ml) compared to the benign ovarian cyst patients as controls (38 ng/ml, 5–72 ng/ml) values correlating with the stage of disease and the extent of residual tumor mass. No significant correlation between CA125 and RANTES in the serum was observed in either the controls or the ovarian cancer patients. Using a RANTES cutoff of 45 ng/ml and a CA125 cutoff of 35 units/ml, when either marker was elevated, the specificity improved 94%.

Conclusion.

Our study suggest that preoperative serum RANTES levels may be useful in differentiating benign ovarian tumors from malignancy correlating with the extent of the disorder.

Introduction

Human epithelial cancers contain a significant number of host leukocytes, mainly macrophages and lymphocytes, and express a complex network of cytokines and chemokines [1]. The C–C chemokines, including macrophage inflammatory protein-1 (MIP-1), monocyte chemoattractant protein-1 (MCP-1), and regulated upon activation, normal T-cell expressed and secreted (RANTES), are the major determinants of macrophage and lymphocyte infiltration in carcinomas of the breast, ovary, and cervix [2], [3].

Recent findings suggest that RANTES is produced by several tumor cells [4] including the breast tumor cells, and then its receptors, CCR1 and CCR5, are expressed by the leukocyte infiltrate and that chemokine receptor antagonist may provide novel strategies in breast cancer prevention and treatment [5]. It has also been demonstrated that high plasma RANTES levels are correlated with advanced breast cancer and that breast tumor-cell-derived RANTES may promote breast cancer progression and metastasis [6].

The C–C chemokines and their receptors have been implicated in the migration of ovarian cancer cells [7]. Negus et al. have reported the production of MCP-1 by human ovarian cancer cells and that demonstrated the presence of a chemokine gradient between ascites and plasma [8]. Expression of RANTES and MIP-1 in ovarian cancer [9] and the loss of tumorigenicity in vivo by RANTES secretion by gene-modified tumor cells [10] have been demonstrated. Although RANTES could be used as a prognostic indicator in both breast and cervical cancers [6], to our knowledge, there are no previous reports of serum RANTES levels in ovarian cancer patients. The most commonly used serum marker for ovarian cancer is CA125, which is found elevated in the majority of all ovarian cancers [11], [12]. Thus, we measured serum concentrations of RANTES in benign and malignant ovarian disease patients, studied correlation between CA125 and RANTES in the serum, and then evaluated the utility of preoperative RANTES levels in distinguishing malignant from benign disease.

Section snippets

Patients

Fifty-two women with invasive epithelial ovarian cancer, 6 patients with borderline ovarian tumors of low malignant potential (LMP), 28 patients with benign ovarian cysts, and 12 healthy women as controls, were enrolled between 1997 and 2004, and the preoperative serum samples were reviewed in this study. The study protocol was approved by the Institutional Review Board of Nagoya City University, and informed consent was obtained from all of the study subjects. Patients with inflammatory

Results

The malignant group (n = 52, 54 ± 1.9: mean age ± SEM), borderline group (n = 6, 52 ± 5.3), benign group (n = 28, 50 ± 4.3), and normal control group (n = 12, 49 ± 4.9) were matched for age. Serum samples from the women with ovarian cancer (n = 52) contained significantly higher (P = 0.0003) concentrations of RANTES (median 53 ng/ml, interquartile range 23–104 ng/ml) than those of the group with benign ovarian disease (38 ng/ml, 5–72 ng/ml) by the Mann–Whitney test (Table 1 and Fig. 1).

Table 2

Discussion

We found concentrations of RANTES in serum to be significantly elevated in women with ovarian cancer, as compared to benign ovarian cyst patients, correlating with the extent of the disease. Higher concentrations of RANTES were also observed in the patients with residual tumor mass than without it. No significant correlations between CA125 and RANTES were observed in either the controls or the ovarian cancer patients by Spearman's rank correlation. Using a RANTES cutoff of 45 ng/ml and a CA125

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Elevated serum RANTES levels in patients with ovarian cancer correlate with the extent of the disorder

Abstract

Objective.

Methods.

Results.

Conclusion.

Introduction

Section snippets

Patients

Results

Discussion

Semin. Cancer Biol.

Lancet

Cytokine Growth Factor Rev.

Cytokine

The CC chemokine RANTES in breast carcinoma progression: regulation of expression and potential mechanisms of promalignant activity

Cancer Res.

A chemokine receptor antagonist inhibits experimental breast tumor growth

Cancer Res.

Correlation of tissue and plasma RANTES levels with disease course in patients with breast or cervical cancer

Clin. Cancer Res.

Epithelial cancer cell migration: a role for chemokine receptors?

Cancer Res.

The detection and localization of monocyte chemoattractant protein-1 (MCP-1) in human ovarian cancer

J. Clin. Invest.

RANTES secretion by gene-modified tumor cells results in loss of tumorigenicity in vivo: role of immune cell subpopulations

Hum. Gene Ther.