Objectives: Lymph node metastasis affects the initial treatment strategy for cervical cancer and is hard to be diagnosed in clinical practice.This paper aims to explore the relationship between calcium-binding A9 (S100A9) and lymph node metastasis (LNM) in cervical cancer, and to determine the predictive value of S100A9 for LNM in cervical cancer.
Methods: We performed a retrospective cohort study and collected the pathological data, follow-up data, and paraffin tissue samples of 99 patients with cervical cancer who underwent modified extensive or extensive hysterectomy plus pelvic lymphadenectomy at the Department of Gynecology, Xiangya Hospital, Central South University from January 2013 to December 2018. Immunohistochemistry was used to detect the expression of S100A9 in cervical cancer tissues, and the correlation between S100A9 expression and LNM of cervical cancer, or clinicopathological characteristics were analyzed. The receiver operating characteristic (ROC) curve was used to establish a predictive model for LNM of cervical cancer, and Chi-square test of four-grid table was used to evaluate the diagnostic value of S100A9 for LNM in cervical cancer.
Results: The expression of S100A9 was significantly correlated with LNM. The S100A9 immunohistochemical semi-quantitative score of the LNM group was significantly higher than that in the non-lymph node metastasis group (P<0.001). Moreover, the expression of S100A9 was significantly correlated with histological type, stromal invasion, lymphatic vessel invasion, or LNM (P<0.05). The cut-off of the ROC curve for predicting LNM was 5, with the Youden index of 0.649 and the area under the ROC curve of 0.863. The disease-free survival and overall survival in the S100A9 positive group were significantly shorter than those in the negative group (P<0.05). S100A9 alone had a sensitivity of 71.4%, a specificity of 91.5%, and an accuracy of 85.1% for diagnosing LNM. Imaging had a sensitivity of 32.1%, a specificity of 74.6%, and an accuracy of 60.9%. Combination of S100A9 with image examination in parallel test had a sensitivity of 85.7%, a specificity of 71.2%, and an accuracy of 75.9%, while combination of S100A9 and image examination in serial test had a sensitivity of 17.9%, a specificity of 98.3%, and an accuracy of 72.4%.
Conclusions: S100A9 may be associated with LNM in cervical cancer. S100A9 shows a promising perspective in predicting LNM in cervical cancer. Combination of S100A9 and image examination in serial test has a high specificity for LNM.
目的: 淋巴结转移影响宫颈癌初始治疗方式的选择，而临床上诊断困难。本研究旨在探讨钙联蛋白A9(S100A9)与宫颈癌淋巴结转移的关系以及S100A9对宫颈癌淋巴结转移的预测价值。方法: 采用回顾性队列研究方法收集2013年1月至2018年12月在中南大学湘雅医院妇科行改良广泛或广泛子宫切除术+盆腔淋巴结清扫术的99例宫颈癌患者的临床病理资料、预后随访资料及石蜡组织标本。采用免疫组织化学方法检测宫颈癌患者组织中S100A9表达情况，分析S100A9表达与宫颈癌淋巴结转移及临床病理特征的相关性；采用受试者工作特征(receiver operating characteristic，ROC)曲线，建立宫颈癌淋巴结转移的预测模型，采用四格表资料的χ2检验评估S100A9对宫颈癌淋巴结转移的诊断价值。结果: S100A9的表达与宫颈癌患者有无淋巴结转移显著相关，有淋巴结转移组的S100A9免疫组织化学半定量评分显著高于无转移组(P<0.001)，且S100A9的表达也与组织类型(P<0.001)、间质浸润深度(P=0.005)、有无脉管浸润(P<0.001)相关。ROC曲线计算S100A9表达预测宫颈癌淋巴结转移的截断值为5，约登指数0.649，ROC曲线下面积为0.863。S100A9阳性组无病生存期和总生存时间明显短于S100A9阴性组(分别P=0.006和 P=0.025)。S100A9单独诊断淋巴结转移的灵敏度为71.4%，特异度为91.5%，准确度为85.1%；影像学诊断淋巴结转移的灵敏度为32.1%，特异度为74.6%，准确度为60.9%；S100A9联合影像学并联试验诊断淋巴结转移(二者其一阳性)的灵敏度为85.7%，特异度为71.2%，准确度为75.9%；S100A9联合影像学串联试验诊断淋巴结转移(二者均阳性)的灵敏度为17.9%，特异度为98.3%，准确度为72.4%。结论: S100A9可能与宫颈癌淋巴结转移有关；S100A9对宫颈癌淋巴结转移具有预测价值；S100A9联合影像学(串联试验)对淋巴结转移的诊断具有高度特异性。.
Keywords: S100A9; cervical cancer; clinicopathological features; imaging; lymph node metastasis.