摘要
目的评估肿瘤浸润淋巴细胞(tumor-infiltrating lymphocytes,TIL)在实施初次肿瘤减灭术(primary debulking surgery,PDS)与新辅助化疗的卵巢高级别浆液性腺癌中表达差异以及与临床特征、预后的关系.方法收集四川大学华西第二医院2013年1月至2016年1月138例卵巢高级别浆液性腺癌患者的肿瘤石蜡标本构建组织芯片,其中PDS组84例和新辅助化疗组54例.通过免疫组织化学染色的方法检测CD3+、CD4+及CD8+TIL在癌组织中的浸润水平,比较其在PDS组与新辅助化疗组间的差异并评估其与临床特征及预后的关系.结果新辅助化疗与PDS两组间肿瘤内CD3+、CD4+、CD8+TIL浸润差异无统计学意义(P>0.05),且在PDS组中CD3+、CD4+及CD8+TIL与患者的年龄、月经状态、国际妇产科联盟分期、化疗敏感性也无相关性(P>0.05),然而在新辅助化疗组中CD8+TIL与化疗敏感性密切相关(P=0.01).单因素生存分析发现,PDS组与新辅助化疗组肿瘤组织中CD8+TIL高浸润患者预后均较好(P=0.030;P=0.032),此外,新辅助化疗组中CD3+TIL高浸润患者预后也较好(P=0.019).多因素生存分析证实,CD8+TIL(HR=0.369,95%CI=0.176~0.772,P=0.008)是卵巢高级别浆液性腺癌独立的预后因素.结论 CD8+TIL是卵巢高级别浆液性腺癌患者的预后独立影响因素;而对于接受新辅助化疗的患者而言,CD8+TIL还能作为术后化疗敏感性的评估指标.
Objective To compare intratumoral tumor-infiltrating lymphocytes (TIL) in a cohort of high-grade serous ovarian carcinoma patients between those who treated with neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS), and to determine the clinical and prognostic significance of TIL in high-grade serous ovarian carcinoma. Methods Tissue microarrays and immunohistochemistry were used to assess the quantity of CD3+, CD4+ and CD8+ lymphocytes in tumor tissue from 138 high-grade serous ovarian carcinoma (PDS n=84, NACT n=54) which were collected from January 2013 to January 2016 at West China Second University Hospital, Sichuan University. TIL was analysed in two predefined groups of low and high TIL. The associations between clinical features and TIL were evaluated by χ2 test or Fisher′s exact test, and Kaplan-Meier survival analysis and Cox proportional hazards regression model were used for the association between the amounts of TIL and progression free survival. Results There was no difference in TIL/HPF (high-power field) counting in tumor tissue between PDS and NACT (P>0.05), and in the PDS cohort, CD3+, CD4+ and CD8+TIL were not associated with any clinical features like age, FIGO stage, tumor size and chemotherapy sensitivity, however, in the NACT cohort, CD8+TIL was strongly associated with chemotherapy sensitivity. The univariable analysis supported that high CD8+TIL in tumor tissue was associated with longer progression free survival both in the PDS and NACT cohort(P=0.030, P=0.032), but not CD4+TIL, in the NACT cohort, high CD3+TIL were also associated with longer progression free survival (P=0.019). Finally, in multivariate analysis, only the high CD8+TIL had prognostic significance (HR=0.369, 95%CI=0.176-0.772, P=0.008). Conclusion High CD8+lymphocytes density in tumor tissue was significantly associated with improved progression free survival in high-grade serous ovarian carcinoma. Besides, the CD8+lymphocytes density could be served as a potential marker of the chemotherapy sensitivity
作者
黄星铭
张燕
徐炼
王梅
王巍
Huang Xingming;Zhang Yan;Xu Lian;Wang Mei;Wang Wei(Department of Pathology, West China Second University Hospital, Sichuan University,Laboratory of Molecular and Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China)
出处
《中华病理学杂志》
CAS
CSCD
北大核心
2019年第8期610-614,共5页
Chinese Journal of Pathology
基金
四川省科技厅支撑项目(2014SZ0001).
关键词
卵巢肿瘤
淋巴细胞
肿瘤浸润
预后
Ovarian neoplasms
Lymphocytes, tumor-infiltrating
Prognosis
