收稿日期: 2019-12-09
网络出版日期: 2020-04-18
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
Received date: 2019-12-09
Online published: 2020-04-18
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)
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.
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 . DOI: 10.19723/j.issn.1671-167X.2020.02.008
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.
| [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. |
/
| 〈 |
|
〉 |
