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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"

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