Chemokine receptor CXCR4 expression and prognosis in patients with metastatic prostate cancer

Abstract

The chemokine receptor CXCR4 has been reported to be aberrantly expressed in human cancers and has also been shown to participate in the development of cancer metastasis. The present study was carried out to assess immunohistochemically the pattern of CXCR4 expression in patients with metastatic prostate cancer. We analyzed whether there may be an association between CXCR4 expression and prognosis. Fifty-two patients who received hormonal therapy were enrolled. Specimens were obtained from transperineal needle biopsy before treatment, and were stained with antihuman CXCR4 antibody. We also evaluated the pathological grade, extent of bony metastasis, clinical response to hormonal therapy, and patient prognosis. CXCR4 was detected in 94.2% patients. Its expression showed no association with pathological grade, extent of bony metastasis, or clinical response to hormonal therapy. Patients with a high expression of CXCR4 in tumors had poorer cancer-specific survival than those with low expression of CXCR4. CXCR4 expression is a useful prognostic factor for patients with metastatic prostate cancer treated with androgen-withdrawal therapy.

Figure 1

CXCR4 expression in prostate cancer (with bone metastasis) (×200). The evaluations were recorded as the percentage of positively stained tumor cells in each of three intensity categories: sporadic, 0–5%; focal, 6–50%; and diffuse, 51–100%.

Figure 2

Kaplan–Meier cause‐specific survival curves for patients with metastatic prostate cancers relative to clinicopathological features. (a) Cancer‐specific survival according to pretreatment Gleason score. Solid and dotted lines represent Gleason score <8 (n = 21) and = 8 (n = 31), respectively; P = 0.0025. (b) Cancer‐specific survival according to extent of disease (EOD). Solid and dotted lines represent EOD 0–2 (n = 32) and EOD 3–4 (n = 20), respectively; P = 0.0891. (c) Cancer‐specific survival according to clinical response to hormonal therapy. Solid and dotted lines represent complete response (n = 32), and partial response, no change, and progressive disease (n = 20), respectively; P = 0.0257. (d) Cancer‐specific survival according to CXCR4 expression. Solid and dotted lines represent CXCR4 expression of low (sporadic and focal, n = 34) and high (diffuse, n = 18), respectively; P = 0.0159.