宫颈腺癌细胞CXCR4/CXCL12过表达与淋巴结转移和慢性炎症的关系

Correlation of CXCR4/CXCL12 Overexpression to Lymph Node Metastasis and Chronic Inflammation in Cervical Adenocarcinoma

背景与目的:CXCL12是一种炎症趋化因子,CXCR4是其特异性受体。有文献报道CXCR4参与多种恶性肿瘤的转移过程。但CXCR4/CXCL12在宫颈腺癌细胞中表达的意义鲜见报道。本研究探讨CXCR4/CXCL12在宫颈腺癌细胞中过表达与淋巴结转移及宫颈慢性炎症程度的相关性。方法:收集35例行子宫颈癌根治术的ⅠB1～ⅡB期宫颈腺癌标本,其中有淋巴结转移组8例,无淋巴结转移组27例。组织切片行CXCR4和CXCL12免疫组化染色及HE染色,90%以上肿瘤细胞强着色定义为过表达。采用FisherWs精确概率检验法、卡方检验及Pearson相关检验分析结果。结果:35例均有不同数量肿瘤细胞表达CXCR4。有淋巴结转移组CXCR4过表达率(62.50%,5/8)高于无淋巴结转移组(22.00%,6/27),P<0.05。临床ⅠB期有淋巴结转移组CXCR4过表达率(33.33%,1/3)高于无淋巴结转移组(26.01%,6/23),但P>0.05;临床ⅡB期,有淋巴结转移组CXCR4过表达率高于无淋巴结转移组(80.00%,4/5vs.0.00%,0/4),P<0.05。CXCR4过表达预测淋巴结转移的阳性预测值为45.45%,阴性预测值为87.50%。35例中33例有数量不等的肿瘤细胞表达CXCL12。无论有淋巴结转移组或无淋巴结转移组,临床Ⅱ期病例CXCL12过表达率均明显高于ⅠB期(0.00%vs.80.00%,21.73%vs.75.00%),P<0.05。23例临床ⅠB期无淋巴结转移组,CXCR4过表达率与CXCL12过表达率呈正相关(P<0.05);但在ⅠB期有淋巴结转移组(3例)及ⅡB期(9例)病例组,两者间无相关性。35例病例均伴有不同程度慢性炎症,炎性浸润主要为淋巴细胞。CXCL12过表达率与宫颈慢性炎症浸润程度无相关性,P>0.05。结论:宫颈腺癌细胞CXCR4过表达提示具有较高淋巴结转移潜能。随着肿瘤进展,CXCL12过表达率也随之升高。宫颈腺癌中慢性炎症细胞可能由其它趋化因子吸引所致,而非CXCL12。

BACKGROUND ＆ OBJECTIVE： CXCL12 is a kind of chemokine. CXCR4, the specific receptor of CXCL12, is involved in metastasis of tumors. CXCR4/CXCL12 expression in cervical adenocarcinoma has seldom been reported. This study was to investigate the correlation of CXCR4/CXCL12 overexpression to lymph node metastasis and chronic inflammation in cervical adenocarcinoma. METHODS, CXCR4 and CXCL12 immunohistochemical staining and HE staining were performed in 35 specimens of cervical adenocarcinoma, including 8 with lymph node metastasis and 27 without. Marked expression of CXCR4 or CXCL12 observed in more than 90% tumor cells was defined as overexpression. Fisher＇ s exact test, Chi-square test, and Pearson correlation test were used to analyze the results. RESULTS, All 35 specimens of cervical adenocarcinoma expressed CXCR4. The overexpression rate of CXCR4 was significantly higher in the cases with lymph node metastasis than in those without （62.50% vs. 22.00%, P〈0.05）, slightly higher in the Ⅰ B cases with lymph node metastasis than in those without （33.33% vs. 26.01%, P〉0.05）, and significantly higher in the Ⅱ B cases with lymph node metastasis than in those without （80.00% vs. 0.00%, P〈0.05）. The positive predictive value of CXCR4 overexpression to assess lymph node metastasis was 45.45%, and the negative predictive value was 87.50%. A variable number of tumor cells in 33 specimens expressed CXCL12. The overexpression rate of CXCL12 was significantly higher in Ⅰ B cases than in Ⅱ B cases either in tumors with lymph node metastasis （0.00% vs. 80.00%, P〈0.05） or without （21.73% vs. 75.00%, P〈0.05）. CXCR4 overexpression was positively correlated to CXCL12 overexpression in the 23 Ⅰ B cases without lymph node metastasis; but the correlation did not exist in the 3 Ⅰ B cases with lymph node metastasis and the 9 Ⅱ B cases. All the 35 specimens were accompanied with chronic inflammation; the infiltrates were mainly lymphocytes. CXCL12 overexpression was not correlated to the infiltration degree of chronic inflammation. CONCLUSIONS. CXCR4 overexpression indicates a higher lymph node metastasis potential of cervical adenocarcinoma. The overexpression rate of CXCL12 is increasing by the progression of tumors. The chronic inflammatory cells in cervical adenocarcinoma are not attracted by CXCL12.