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Journal of Peking University (Health Sciences) ›› 2020, Vol. 52 ›› Issue (2): 240-246. doi: 10.19723/j.issn.1671-167X.2020.02.008

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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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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

CLC Number: 

  • R735.4

Figure 1

Flowchart of case screening PMP, pseudomyxoma peritonei; CRS, cytoreductive surgery; HIPEC, hyperthermic intraperitoneal chemotherapy; LMCP, low-grade mucinous carcinoma peritonei; HMCP, high-grade mucinous carcinoma peritonei."

Figure 2

Flowchart of histopathological quantitative analysis A1-A2, HE staining pathological sections were prepared from pseudomyxoma peritonei tumor tissues; B1-B2, pthological image acquisition; C1-C2, Image-pro plus was used to achieve the segmentation of tumor and stroma. B2, C1-C2, LMCP (×100)"

Table 1

Primary antibodies used for immunohistochemistry"

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

Table 2

Correlation between TSR and clinicopathological characteristics of PMP"

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

Figure 3

Histopathological features of LMCP Abundant mucus and scanty tumor epithelial cells in the mucous pool. Tumor cells are monolayer or in the shape of strips (A: red arrow), islands (B: black arrow) or clusters (C: green arrow). Minimal cytological atypia, small and regular nucleus and few mitosis (D: blue arrow). A-C, ×200; D, ×400."

Figure 4

Histopathological features of HMCPRelatively more cellular. Tumor cells are in the shape of islands (A: red arrow), cribriform (B: black arrow) and gland-like (C: green arrow) of tumor cells. High-grade cytological atypia, prominent nucleoli and numerous mitosis (D: blue arrow). A-C, ×200; D, ×400."

Figure 5

Kaplan-Meier survival analysis stratified by TSR"

[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.
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