趋化因子CXCL12及其受体CXCR4在人上皮性卵巢癌中的表达：肿瘤进展的独立预后因素

Expression of chemokine CXCL12 and its receptor CXCR4 in human epithelial ovarian cancer: an independent prognostic factor for tumor progression.

作者信息

Jiang Yu-Ping, Wu Xiao-Hua, Shi Bin, Wu Wen-Xin, Yin Gui-Ran

机构信息

Department of Obstetrics and Gynecology, the Second Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

Gynecol Oncol. 2006 Oct;103(1):226-33. doi: 10.1016/j.ygyno.2006.02.036. Epub 2006 May 2.

DOI:10.1016/j.ygyno.2006.02.036

PMID:16631235

Abstract

OBJECTIVES

Chemokine CXCL12 and its unique receptor CXCR4 have been recently implicated in cancer metastasis. Our goal was to explore expression of CXCL12 and CXCR4 protein in normal ovarian surface epithelium, primary tumors and paired metastases of epithelial ovarian cancer as well as its association with clinicopathological features. We also wanted to test if expression of CXCR4 has prognostic value in epithelial ovarian cancer patients.

METHOD

Sections from 6 normal ovarian surface epithelium, 44 primary epithelial ovarian tumors and 30 paired metastatic tumors in omentum were evaluated for CXCL12 and CXCR4 expression using immunohistochemistry (IHC).

RESULTS

All samples of normal ovarian surface epithelium were negative for CXCL12 and CXCR4 protein. Ovarian cancer cells mainly showed cytoplasmic staining of CXCL12 and CXCR4. CXCL12 and CXCR4 staining were detected in 40/44 (91%) and 26/44 (59%) patients with primary epithelial ovarian tumors respectively. CXCR4 expression in primary tumors had no significant correlation with lymph nodes metastasis. However, if we combined CXCR4 expression in primary tumors with metastatic tumors, a significant correlation with lymph nodes metastasis was found (P = 0.018). The intensity of CXCL12 staining correlated with ascites (P = 0.014). The rate of CXCR4 expression in refractory and recurrent group (81% versus 28%, P = 0.0008) was significantly higher than that in no-recurrent group. After a median follow-up of 37 months, CXCR4 expression was found associated with an unfavorable prognosis with significantly reduced median disease progression-free survival and overall survival of 15 and 27 months (P = 0.0004, P = 0.017) respectively. Median time-to-event was not reached in patients with negative CXCR4 staining. In multivariate analysis, CXCR4 expression and residual tumor size emerged as independent prognostic factors in epithelial ovarian cancer patients.

CONCLUSIONS

This article provides the first evidence that CXCR4 expression could be an independent prognostic factor for epithelial ovarian cancer patients.

摘要

目的

趋化因子CXCL12及其独特受体CXCR4最近被认为与癌症转移有关。我们的目标是探讨CXCL12和CXCR4蛋白在正常卵巢表面上皮、原发性肿瘤及上皮性卵巢癌配对转移灶中的表达情况，以及它们与临床病理特征的关系。我们还想检测CXCR4的表达在上皮性卵巢癌患者中是否具有预后价值。

方法

采用免疫组织化学（IHC）法评估6例正常卵巢表面上皮、44例原发性上皮性卵巢肿瘤及30例配对大网膜转移瘤切片中CXCL12和CXCR4的表达。

结果

所有正常卵巢表面上皮样本的CXCL12和CXCR4蛋白均为阴性。卵巢癌细胞主要表现为CXCL12和CXCR4的细胞质染色。原发性上皮性卵巢肿瘤患者中，CXCL12和CXCR4染色阳性率分别为40/44（91%）和26/44（59%）。原发性肿瘤中CXCR4的表达与淋巴结转移无显著相关性。然而，若将原发性肿瘤和转移瘤中的CXCR4表达合并分析，则发现与淋巴结转移有显著相关性（P = 0.018）。CXCL12染色强度与腹水相关（P = 0.014）。难治复发组中CXCR4的表达率（81%对28%，P = 0.0008）显著高于无复发组。中位随访37个月后，发现CXCR4表达与不良预后相关，疾病无进展生存期和总生存期的中位数显著缩短，分别为15个月和27个月（P = 0.0004，P = 0.017）。CXCR4染色阴性的患者未达到事件发生的中位时间。多因素分析显示，CXCR4表达和残留肿瘤大小是上皮性卵巢癌患者的独立预后因素。