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北京大学学报（医学版） ›› 2020, Vol. 52 ›› Issue (2): 240-246. doi: 10.19723/j.issn.1671-167X.2020.02.008

• 论著 • 上一篇    下一篇

肿瘤间质比评估阑尾来源腹膜假黏液瘤的临床价值

马茹1,李鑫宝1,闫风彩2,林育林1,李雁1,2,△()   

  1. 1. 首都医科大学附属北京世纪坛医院 腹膜肿瘤外科,北京 100038
    2. 首都医科大学附属北京世纪坛医院 病理科,北京 100038
  • 收稿日期:2019-12-09 出版日期:2020-04-18 发布日期:2020-04-18
  • 通讯作者: 李雁 E-mail:liyansd2@163.com
  • 基金资助:
    北京市医院管理局"登峰"人才培养计划(DFL20180701);首都临床特色应用研究与成果推广项目(Z161100000516077);北京市优秀人才培养资助集体项目(2017400003235J007);北京市自然科学基金(7172108);北京市卫生与健康科技成果和适宜技术推广项目(2018-TG-27);北京市自然科学基金(7172108);北京市卫生与健康科技成果和适宜技术推广项目(2018-TG-27)(2018-TG-27)

Clinical evaluation of tumor-stroma ratio in pseudomyxoma peritonei from the appendix

Ru MA1,Xin-bao LI1,Feng-cai YAN2,Yu-lin LIN1,Yan LI1,2,△()   

  1. 1. Department of Peritoneal Cancer Surgery, Beijing 100038, China
    2. Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
  • Received:2019-12-09 Online:2020-04-18 Published:2020-04-18
  • Contact: Yan LI E-mail:liyansd2@163.com
  • Supported by:
    Supported by Beijing Municipal Administration of Hospitals' Ascent Plan(DFL20180701);Special Fund for the Capital Characteristic Clinical Medicine Development Project(Z161100000516077);Beijing Municipal Grant for Medical Talents Group on Peritoneal Surface Oncology(2017400003235J007);Beijing Natural Science Foundation(7172108);Beijing Natural Science Foundation(2018-TG-27);Beijing Natural Science Foundation(7172108);Health Science Promotion Project of Beijing(2018-TG-27)

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摘要：

目的 研究肿瘤间质比(tumor-stroma ratio,TSR)对腹膜假黏液瘤(pseudomyxoma peritonei,PMP)疾病进展及预后的影响.方法: 收集北京世纪坛医院2015年6月至2019年6月行肿瘤细胞减灭术加腹腔热灌注化疗治疗,且病例资料完善的PMP患者,利用Image-Pro Plus定量研究其HE病理图像的TSR,分析TSR与PMP临床病理特征,免疫组织化学特征和预后的关系.结果: 纳入30例PMP患者,男16例(53.3%),女14例(46.7%),平均年龄(54.9 ± 2.3)岁;组织病理学分级为腹膜低级别黏液癌(low-grade mucinous carcinoma peritonei,LMCP)15例(50.0%)和腹膜高级别黏液癌(high-grade mucinous carcinoma peritonei,HMCP)15例(50.0%);脉管癌栓者4例(13.3%),神经侵犯者3例(10.0%),淋巴结转移者4例(13.3%);中位腹膜癌指数(peritoneal cancer index,PCI)评分36分(范围3~39分),中位TSR为8%(范围2%~24%),TSR≤10%者19例(63.3%),TSR>10%者11例(36.7%).免疫组织化学染色结果显示,Ki67标记率≤50%者16例(53.3%),>50%者14例(46.7%);p53突变率为56.7%;错配修复(mismatch repair,MMR)基因相关蛋白缺失率为11.8%;MUC2,MUC5AC,CDX2,CK7与CK20的表达率分别为66.7%,100.0%,82.6%,56.0%和92.3%.TSR与组织病理学分级,神经侵犯,Ki67标记率,p53突变密切相关(P<0.05).截至末次随访时间,21例(70.0%)患者死亡,9例(30.0%)患者存活,其中6例患者带瘤生存.患者中位生存期为12.7个月(95%CI:10.4~11.5个月),1,2,3年生存率分别为60.5%,32.3%,27.7%.生存分析显示,中位总生存期在TSR≤10%组为19.4个月(95%CI:3.0~35.9个月),TSR>10%组为12.6个月(95%CI:0.7~24.5个月),差异有统计学意义(χ 2 = 3.996,P=0.046).结论: TSR与PMP的组织病理学分级,肿瘤增生,侵袭行为,患者预后有正相关性,可作为评估PMP预后的新指标.

关键词: 腹膜假黏液瘤, 肿瘤间质比, 病理学, 临床, 免疫组织化学, 预后

Abstract:

Objective: To evaluate the effect of tumor-stroma ratio (TSR) on disease progression and prognosis of pseudomyxoma peritonei (PMP) from the appendix.Methods: The study included 30 PMP patients with complete individual patient data, who underwent cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Beijing Shijitan Hospital. Image-Pro Plus was used to quantitatively analyze the proportion of tumor and stromal areas in hematoxylin-eosin staining pathological images, from which TSR was derived. Correlation studies were conducted to evaluate the relationships between TSR and clinicopathological features, immunohistochemical characteristics, and prognosis of PMP.Results: Among 30 PMP patients, there were 16 males (53.3%) and 14 females (46.7%), with the mean age of (54.9±2.3) years. There were 15 cases (50.0%) of low-grade mucinous carcinoma peritonei (LMCP) and high-grade mucinous carcinoma peritonei (HMCP), respectively, with vascular tumor emboli occurring in 4 cases (13.3%), nerve invasion occurring in 3 cases (10.0%), and lymphatic metastasis occurring in 4 cases (13.3%). The median peritoneal cancer index (PCI) score was 36 (range: 3-39). The median TSR was 8% (range: 2%-24%), with TSR≤10% in 19 cases (63.3%) and TSR>10% in 11 cases (36.7%). Immunohistochemistry showed that 16 cases (53.3%) had Ki67 label index ≤ 50% and 14 cases (46.7%) > 50%. The mutation rate of p53 was 56.7% and the loss rate of MMR protein was 11.8%. In addition, the expression rates of MUC2, MUC5AC, CDX2, CK7, and CK20 were 66.7%, 100.0%, 82.6%, 56.0%, and 92.3%, respectively. There were significant correlations between TSR and histopathological types, nerve invasion, Ki67 label index, and p53 mutation (P<0.05 for all). At the end of the last follow-up, 21 patients (70.0%) died and 9 patients (30.0%) survived, including 6 patients survived with tumor. The median overall survival (OS) was 12.7 months (95%CI: 10.4-11.5 months), and the 1-, 2-, and 3-year survival rates were 60.5%, 32.3%, and 27.7%, respectively. The median OS was 19.4 months (95%CI: 3.0-35.9 months) in the TSR≤10% group, versus 12.6 months (95%CI: 0.7-24.5 months) in the TSR>10% group (χ 2=3.996, P=0.046).Conclusion: TSR is correlated with histopathological types, tumor proliferation, invasion behaviors and prognosis of PMP, thus could be a new prognostic indicator for PMP.

Key words: Pseudomyxoma peritonei, Tumor-stroma ratio, Pathology, clinical, Immunohistochemistry, Prognosis

中图分类号: 

  • R735.4

图1

病例筛选流程图"

图2

组织病理定量分析工作流程"

表1

免疫组织化学染色的一抗"

Target Supplier Catalog number Dilution
Ki67 OriGene UMAB107 Ready to use
p53 OriGene DO7 Ready to use
MUC2 OriGene MRQ-18 Ready to use
MUC5AC OriGene MRQ-19 Ready to use
MLH1 OriGene ES05 Ready to use
MLH2 OriGene 25D12 Ready to use
MLH6 OriGene EP49 Ready to use
PMS2 OriGene EP51 Ready to use
CDX2 OriGene EP25 Ready to use
CK7 OriGene EP16 Ready to use
CK20 OriGene EP23 Ready to use

表2

TSR与PMP临床病理特征的关系"

Items n(%) TSR P
≤10% >10%
Gender 0.707
Male 16 (53.3) 11 5
Female 14 (46.7) 8 6
Age 0.454
≤54 years old 17 (56.7) 12 5
>54 years old 13 (43.3) 7 6
Previous surgical history 0.126
Yes 26 (86.7) 18 8
No 4 (13.3) 1 3
Pathological types <0.001
LMCP 15 (50.0) 15 0
HMCP 15 (50.0) 4 11
Vascular tumor emboli 0.126
Yes 4 (13.3) 1 3
No 26 (86.7) 18 8
Nerve invasion 0.041
Yes 3 (10.0) 0 3
No 27 (90.0) 19 8
Lymphatic metastasis 0.611
Yes 4 (13.3) 2 2
No 26 (86.7) 17 9
PCI scores 0.702
≤37 20 (66.7) 12 8
>37 10 (33.3) 7 3
CC scores 0.063
0-1 12 (40.0) 5 7
2-3 18 (60.0) 14 4

图3

LMCP的组织病理学特征"

图4

HMCP的组织病理学特征"

图5

TSR分组的Kaplan-Meier单因素生存分析"

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ISSN 1671-167X
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