肿瘤间质比评估阑尾来源腹膜假黏液瘤的临床价值

doi:10.19723/j.issn.1671-167X.2020.02.008

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

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. 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 LI^1,^2,^△()

^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)

摘要/Abstract

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

马茹,李鑫宝,闫风彩,林育林,李雁. 肿瘤间质比评估阑尾来源腹膜假黏液瘤的临床价值[J]. 北京大学学报（医学版）, 2020, 52(2): 240-246.

Ru MA,Xin-bao LI,Feng-cai YAN,Yu-lin LIN,Yan LI. Clinical evaluation of tumor-stroma ratio in pseudomyxoma peritonei from the appendix[J]. Journal of Peking University (Health Sciences), 2020, 52(2): 240-246.

图/表 7

图1

图2

表1

表2

图3

图4

图5

参考文献 19

[1]	李雁, 许洪斌, 彭正 , 等. 肿瘤细胞减灭术加腹腔热灌注化疗治疗腹膜假黏液瘤专家共识[J]. 中华医学杂志, 2019,99(20):1527-1535.
[2]	Carr NJ, Cecil TD, Mohamed F , et al. A consensus for classification and pathologic reporting of pseudomyxoma peritonei and associated appendiceal neoplasia: The results of the peritoneal surface oncology group international (psogi) modified delphi process[J]. Am J Surg Pathol, 2016,40(1):14-26.
[3]	李鑫宝, 林育林, 姬忠贺 , 等. 肿瘤细胞减灭术加腹腔热灌注化疗治疗腹膜假黏液瘤182例分析[J]. 中国肿瘤临床, 2018,45(18):943-949.
[4]	Mohamed F, Gething S, Haiba M , et al. Clinically aggressive pseudomyxoma peritonei: A variant of a histologically indolent process[J]. J Surg Oncol, 2004,86(1):10-15.
[5]	蔡浩, 刘江伟, 黄建钊 . 肿瘤间质比在恶性肿瘤预后评估中的应用研究进展[J]. 山东医药, 2017,57(27):112-114.
[6]	闫风彩, 林育林, 赵洪禹 , 等. 腹膜假黏液瘤155例病理预后因素分析[J]. 中华病理学杂志, 2019,48(7):543-549.
[7]	Budak E, Kahraman DS, Budak A , et al. The proanostic significance of serum ca125 levels with er, pr, p53 and ki-67 expression in endometrial carcinomas[J]. Ginekol Pol, 2019,90(12):675-683.
[8]	李娜, 李佳娜, 郭丰昌 , 等. 腹膜假性黏液瘤误诊为肝硬化腹水1例报告[J]. 临床肝胆病杂志, 2019,35(5):1079-1080.
[9]	李文忠, 潘妍, 刘佳 , 等. 腹膜假黏液瘤12例临床误诊分析[J]. 临床误诊误治, 2017,30(1):18-20.
[10]	Wu JY, Liang CX, Chen MY , et al. Association between tumor-stroma ratio and prognosis in solid tumor patients: A systematic review and meta-analysis[J]. Oncotarget, 2016,7(42):68954-68965.
[11]	Peng C, Liu J, Yang G , et al. The tumor-stromal ratio as a strong prognosticator for advanced gastric cancer patients: Proposal of a new tsnm staging system[J]. J Gastroenterol, 2018,53(5):606-617.
[12]	周全, 石峰, 赵洪禹 , 等. 腹膜黏液性肿瘤的临床病理分析[J]. 中华病理学杂志, 2018,47(3):192-195.
[13]	Li LT, Jiang G, Chen Q , et al. Ki67 is a promising molecular target in the diagnosis of cancer[J]. Mol Med Rep, 2015,11(3):1566-1572.
[14]	Hong B, van den Heuvel APJ, Prabhu VV , et al. Targeting tumor suppressor p53 for cancer therapy: Strategies, challenges and opportunities[J]. Curr Drug Targets, 2014,15(1):80-89.
[15]	Choudry HA, Pai RK, Shuai Y , et al. Impact of cellularity on oncologic outcomes following cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for pseudomyxoma peritonei[J]. Ann Surg Oncol, 2018,25(1):76-82.
[16]	Horvath P, Yurttas C, Birk P , et al. Cellularity in low-grade pseudomyxoma peritonei impacts recurrence-free survival following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy[J]. Langenbecks Arch Surg, 2018,403(8):985-990.
[17]	Choudry HA , O'Malley ME, Guo ZS, et al.Mucin as a therapeutic target in pseudomyxoma peritonei[J]. J Surg Oncol, 2012,106(7):911-917.
[18]	Bhatt A, Mishra S, Prabhu R , et al. Can low grade pmp be divi-ded into prognostically distinct subgroups based on histological features? A retrospective study and the importance of using the appropriate classification[J]. Eur J Surg Oncol, 2018,44(7):1105-1111.
[19]	Valasek MA, Pai RK . An update on the diagnosis, grading, and staging of appendiceal mucinous neoplasms[J]. Adv Anat Pathol, 2018,25(1):38-60.

Metrics

Viewed

Full text

Abstract

Cited

Shared

Discussed

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

Items	n(%)	TSR		P
Items	n(%)	≤10%	>10%	P
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

肿瘤间质比评估阑尾来源腹膜假黏液瘤的临床价值

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

RICH HTML

PDF (PC)

摘要/Abstract

引用本文

使用本文

图/表 7

参考文献 19

相关文章 15

Metrics

本文评价

推荐阅读 10

[1]	薛江,张建运,时瑞瑞,谢晓艳,白嘉英,李铁军. 105例口腔颅颌面部纤维性结构不良的临床病理分析[J]. 北京大学学报（医学版）, 2022, 54(1): 54-61.
[2]	魏慧,罗增,次旦央宗,白玛央金. 高原地区不同海拔高度腹型过敏性紫癜患者临床特征分析[J]. 北京大学学报（医学版）, 2021, 53(6): 1072-1077.
[3]	宋志博,耿研,邓雪蓉,张晓慧,张卓莉. 肌肉骨骼超声在指导银屑病关节炎临床分型中的价值[J]. 北京大学学报（医学版）, 2021, 53(6): 1061-1066.
[4]	王飞,朱翔,贺蓓,朱红,沈宁. 自发缓解的滤泡性细支气管炎伴非特异性间质性肺炎1例报道并文献复习[J]. 北京大学学报（医学版）, 2021, 53(6): 1196-1200.
[5]	刘梅歌,方朴,王严,丛璐,范洋溢,袁远,徐燕,张俊,洪道俊. 远端型遗传性运动神经病8例的临床、病理及遗传学特点[J]. 北京大学学报（医学版）, 2021, 53(5): 957-963.
[6]	高伟波,石茂静,张海燕,吴春波,朱继红. 显著高铁蛋白血症与噬血细胞性淋巴组织细胞增多症的相互关系[J]. 北京大学学报（医学版）, 2021, 53(5): 921-927.
[7]	张梅香,史文芝,刘建新,王春键,李燕,王蔚,江滨. MLL-AF6融合基因阳性急性髓系白血病的临床特征及预后[J]. 北京大学学报（医学版）, 2021, 53(5): 915-920.
[8]	蒋艳芳,王健,王永健,刘佳,裴殷,刘晓鹏,敖英芳,马勇. 前交叉韧带翻修重建术后中长期临床疗效及影响因素[J]. 北京大学学报（医学版）, 2021, 53(5): 857-863.
[9]	肖若陶,刘承,徐楚潇,何为,马潞林. 术前血小板参数与局部进展期肾细胞癌预后[J]. 北京大学学报（医学版）, 2021, 53(4): 647-652.
[10]	于妍斐,何世明,吴宇财,熊盛炜,沈棋,李妍妍,杨风,何群,李学松. 延胡索酸水合酶缺陷型肾细胞癌的临床病理特征及预后[J]. 北京大学学报（医学版）, 2021, 53(4): 640-646.
[11]	赵勋,颜野,黄晓娟,董靖晗,刘茁,张洪宪,刘承,马潞林. 癌栓粘连血管壁对非转移性肾细胞癌合并下腔静脉癌栓患者手术及预后的影响[J]. 北京大学学报（医学版）, 2021, 53(4): 665-670.
[12]	邱敏,费月阳,邓绍晖,刘承,卢剑,何为,陆敏,田晓军,张树栋,马潞林. 后肾腺瘤的诊治经验及文献回顾[J]. 北京大学学报（医学版）, 2021, 53(2): 417-419.
[13]	陈怀安,刘硕,李秀君,王哲,张潮,李凤岐,苗文隆. 炎症生物标志物对输尿管尿路上皮癌患者预后预测的临床价值[J]. 北京大学学报（医学版）, 2021, 53(2): 302-307.
[14]	夏芳芳,鲁芙爱,吕慧敏,杨国安,刘媛. 系统性红斑狼疮伴间质性肺炎的临床特点及相关因素分析[J]. 北京大学学报（医学版）, 2021, 53(2): 266-272.
[15]	高阳旭,孙青,李辉,谢瑶,姚红新,赵卫红. 儿童肝母细胞瘤多学科协作模式下的治疗效果及临床成本[J]. 北京大学学报（医学版）, 2021, 53(1): 200-203.