1、书书书妇女保健/论著卵巢上皮性肿瘤组织中肿瘤坏死因子可溶性肿瘤坏死因子受体表达及与微血管密度相关性郎苏萍，罗陆萍杭州市富阳区妇幼保健院妇科，浙江 杭州 311400基金项目:浙江省医药卫生科技计划(2015KYA243)摘要:目的探讨卵巢上皮性肿瘤组织中肿瘤坏死因子(TNF)、可溶性肿瘤坏死因子受体(sTNF)的表达和微血管密度(MVD)及其与恶性卵巢上皮性肿瘤临床病理因素的关系。方法收集杭州市富阳区妇幼保健院 2017 年 7 月2018 年7 月的恶性卵巢上皮性肿瘤(35 例)、交界性卵巢上皮性肿瘤(32 例)、良性卵巢上皮性肿瘤(34 例)及正常卵巢组织(31 例)，采用免疫组化方法检测
2、 TNF、sTNF的表达和 MVD，分析其相关性及与恶性卵巢上皮性肿瘤临床病理因素之间的关系。结果恶性卵巢上皮性肿瘤组织中的 TNF、sTNF表达及 MVD 值明显高于其他三者(P0.05)，而交界性卵巢上皮性肿瘤高于良性卵巢上皮性肿瘤和正常卵巢组织(P0.05)，良性卵巢上皮性肿瘤及正常卵巢组织差异无统计学意义(P0.05);恶性卵巢上皮性肿瘤中 TNF 表达阳性者 30 例，MVD 值为 20.543.21;TNF 表达阴性者 5 例，MVD 值为 17.982.59，与 TNF 表达阴性者比较差异有统计学意义(P0.05)，TNF 阳性表达与 MVD 值呈正相关(r=0.541，P0.0
3、5);sTNF表达阳性者27 例，MVD 值为20.312.65;sTNF表达阴性者8 例，MVD 值为17.013.33，与 sTNF表达阴性者比较差异有统计学意义(P0.05)，sTNF阳性表达与 MVD 值呈正相关(r=0.484，P0.05)，进一步检测发现 TNF 与sTNF呈正相关关系(r=0.869，P=0.05);有淋巴转移者 TNF、sTNF及 MVD 值较无淋巴转移者阳性表达率显著增高(P0.05);但三者均与卵巢癌的年龄和临床病例分期等无关(P0.05)。结论在卵巢上皮性肿瘤中，TNF 及 sTNF的表达与 MVD 呈正相关且与恶性卵巢上皮性肿瘤的转移有关，并可能成为恶性
4、卵巢上皮性肿瘤临治疗的参考指标。关键词:卵巢上皮性肿瘤;肿瘤坏死因子;可溶性肿瘤坏死因子受体;微血管密度中国图书分类号:737.31文献标识码:A文章编号:1001-4411(2023)05-0777-04;doi:10.19829/j.zgfybj.issn.10014411.2023.05.001Expression of TNF alpha and sTNF in ovarian epithelialtumors and their correlation with microvessel densityLang Suping，LUO LupingDepartment of Gyneco
5、logy，Fuyang Maternal and Child Health Hospital，Hangzhou，Zhejiang 311400，ChinaAbstract:ObjectiveTo investigate the expression of tumor necrosis factoralpha(TNFalpha)and soluble tumor necrosis factorreceptor(sTNF)and microvessel density(MVD)in epithelial ovarian tumors and their relationship with clin
6、icopathological factors ofmalignant epithelial ovarian tumors.Methods35 cases of malignant epithelial ovarian tumors，32 cases of borderline epithelial ovariantumors，34 cases of benign epithelial ovarian tumors and 31 cases of normal ovarian tissues were collected from July 2017 to July 2018 in ourho
7、spital.The expression of TNFa，sTNF and MVD were detected by immunohistochemical method，and the correlation between themand malignant epithelial ovarian tumors was analyzed.The relationship between tumor clinicopathological factors.esultsThe expression ofTNFalpha and sTNF and MVD in malignant epithel
8、ial ovarian tumors were significantly higher than those in other three groups(P0.05)，while borderline epithelial ovarian tumors were higher than benign epithelial ovarian tumors and normal ovarian tissues(P0.05)There was no significant difference between benign epithelial ovarian tumors and normal o
9、varian tissues(P0.05).In malignant epithelialovarian tumors，30 cases were positive for TNFalpha expression，and the MVD value was 20.54 3.21;5 cases were negative forTNFalpha expression，and the MVD value was 17.982.59，which was significantly different from that of negative for TNFalpha expres-sion(P0
10、.05).The positive expression of TNFalpha was positively correlated with MVD value(r=0.541，P0.05);27 cases werepositive for sTNFI expression，and the MVD value was 17.982.59.The MVD value of 8 cases with negative expression of sTNF was17.013.33，which was significantly different from those with negativ
11、e expression of sTNF(P0.05).The positive expression of sT-NF was positively correlated with MVD value(r=0.484，P0.05).Further examination showed that TNFa was positively correla-ted with sTNF(r=0.869，P=0.05).The positive expression rates of alpha，sTNF and MVD were significantly higher thanthose witho
12、ut lymphatic metastasis(P0.05)，but they were not related to the age and clinical stage of ovarian cancer(P0.05).ConclusionIn epithelial ovarian tumors，the positive expression rates of sTNF and MVD were significantly higher than those withoutlymphatic metasta The expression of TNFalpha and sTNF is po
13、sitively correlated with MVD and metastasis of malignant epithelial ovar-ian tumors，and may be a reference index for the treatment of malignant epithelial ovarian tumors.Keywords:Epithelial ovarian tumors;Tumor necrosis factoralpha;Soluble tumor necrosis factor receptor;Microvessel density卵巢恶性肿瘤是妇科恶
14、性肿瘤的第 3 位，其中上皮性卵巢肿瘤约占 90%左右。由于尚未发现卵巢恶777中国妇幼保健2023 年 3 月第 38 卷第 5 期Maternal and Child Health Care of China.March 2023，Vol.38，No.5性肿瘤早期诊断方式，故大部分患者就诊时已经是肿瘤晚期阶段，因此死亡率仍然很高12。随着分子生物学技术的发展，越来越多的研究关注此方面，逐渐认识到一些生长因子与肿瘤之间的相关性。肿瘤坏死因子(TNF)作为一种多功能细胞因子，不但可以直接杀伤敏感的肿瘤细胞，还可以间接地增强免疫活性细胞的功能，并能与其他细胞因子共同抵抗肿瘤，是宿主的最重要防御机
15、制之一34。TNF 主要通过与可溶性肿瘤坏死因子受体(sTNF)介导其生物学活性，sTNF 分为 sTNF和 sTNF，但TNF 大部分情况下均与 sTNF结合，从而抑制TNF 的生物学活性。近年来，大量研究均表明肿瘤的生物学行为与肿瘤组织的微血管密度(MVD)关系密切。因此，本研究旨在探讨上皮性卵巢肿瘤中TNF、sTNF表达及其与 MVD 的关系，为卵巢上皮性肿瘤的早期诊断及预后的判断提供参考依据。现将研究结果报道如下。1资料与方法1.1资料来源选取2017 年7 月2018 年7 月杭州市富阳区妇幼保健院手术治疗的卵巢上皮性肿瘤标本132 例，其中恶性卵巢上皮性肿瘤 35 例，患者平均年龄
16、(51.5 10.86)岁;交界性卵巢上皮性肿瘤32 例，患者平均年龄(52.59.29)岁;卵巢良性上皮性肿瘤 34 例，患者平均年龄(49.8711.30)岁，正常卵巢 31 例，患者平均年龄(54.59.46)岁。全部标本均在手术中送检病理确诊。35 例恶性卵巢上皮性肿瘤中，组织学类性质:浆液性 19 例，黏液性 16 例。临床分期:期 9 例，期 8 例，期13 例，期 5 例。病理分级:G1 级 13 例，G2 级9 例，G3 级 13 例。分化程度:高分 12 化例，中分化 15 例，低分化 18 例，是否有淋巴转移:淋巴转移14 例，无淋巴转移 21 例。1.2方法1.2.1免疫组织化学染色方法4%多聚甲醛溶液常温固定手术切除的标本 1 h，将石蜡切至 4 m 并脱蜡。加入内源性过氧化酶阻断剂，采用双蒸水清洗，分别滴加一抗 TNF、sTNF，阴性对照组滴加PBS，37 孵育 1 h，加入二抗，37 孵育 20 min。具体步骤根据试剂盒说明书进行。DAB 显色 3 5 min，加入双蒸水终止。加一滴苏木素染色 3 5 min，首先用自来水冲洗，随之双蒸水轻轻冲洗，盐酸乙醇