The absence of CCL2 expression in cervical carcinoma is associated with increased survival and loss of heterozygosity at 17q11.2
The absence of CCL2 expression in cervical carcinoma is associated with increased survival and loss of heterozygosity at 17q11.2
复制标题
DOI：
10.1002/path.1918
复制
发表时间：
2006-03
期刊：
影响因子：
--
通讯作者：
H. Zijlmans;G. Fleuren;H. Baelde;P. Eilers;G. Kenter;A. Gorter
中科院分区：
文献类型：
--
作者：
H. Zijlmans;G. Fleuren;H. Baelde;P. Eilers;G. Kenter;A. Gorter
为了确定CCL 2 mRNA表达对宫颈癌患者是有益还是有害，研究了宫颈肿瘤细胞表达该分子、肿瘤相关巨噬细胞数量和临床病理参数（如复发、无复发生存期和患者总生存期）之间的相关性。在来自93名未经治疗的宫颈癌患者的宫颈癌样本中，使用RNA原位杂交定量CCL 2 mRNA表达水平，并使用真实的实时定量RT-PCR进行验证。使用免疫组织化学测定肿瘤相关巨噬细胞的数量。此外，该研究还调查了CCL 2表达的缺乏是否是由于17q11.2（CCL 2基因组）区域附近的遗传改变。宫颈肿瘤细胞的CCL 2 mRNA表达与肿瘤相关巨噬细胞的数量相关（p < 0.001）。CCL 2 mRNA表达缺失（15例样本; 16%）与累积无复发生存期增加（对数秩检验，p = 0.030）、累积总生存期增加（对数秩检验，p = 0.024）、术后手术次数减少、局部和远处复发减少、血管浸润减少和肿瘤尺寸较小（<40 mm）相关。在6个样本中的5个样本中，CCL 2 mRNA表达的缺失与17 q11.2的杂合性缺失（洛）相对应。缺乏肿瘤细胞相关CCL 2 mRNA的宫颈癌患者的累积无复发生存期和累积总生存期增加表明，肿瘤相关巨噬细胞支持肿瘤进展，可能是通过促进血管生成和生长因子的产生。版权所有© 2006大不列颠及爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
To determine whether CCL2 mRNA expression is beneficial or detrimental for cervical cancer patients, the association between the expression of this molecule by cervical tumour cells, the number of tumour‐associated macrophages, and clinicopathological parameters such as recurrence, relapse‐free survival, and overall patient survival was investigated. In cervical cancer samples from 93 untreated cervical cancer patients, the CCL2 mRNA expression level was quantified using RNA in situ hybridization and verified using real‐time quantitative RT‐PCR. The number of tumour‐associated macrophages was determined using immunohistochemistry. Furthermore, the study investigated whether lack of CCL2 expression was due to genetic alterations near the 17q11.2 (CCL2 genomic) region. CCL2 mRNA expression by cervical tumour cells was associated with the number of tumour‐associated macrophages (p < 0.001). Lack of CCL2 mRNA expression (15 samples; 16%) was associated with increased cumulative relapse‐free survival (log rank test, p = 0.030), increased cumulative overall survival (log rank test, p = 0.024), less post‐operative surgery, reduced local and distant recurrence, reduced vascular invasion, and smaller tumour size (<40 mm). The absence of CCL2 mRNA expression corresponded with loss of heterozygosity (LOH) at 17q11.2 in five of six samples. The increased cumulative relapse‐free survival and cumulative overall survival of cervical cancer patients lacking tumour cell‐associated CCL2 mRNA suggest that the tumour‐associated macrophages support tumour progression, presumably by promoting angiogenesis and production of growth factors. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.