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Culture and Imaging of Ex Vivo Organotypic Pseudomyxoma Peritonei Tumor Slices from Resected Human Tumor Specimens
Published on: December 9, 2022
[Clinical evaluation of tumor-stroma ratio in pseudomyxoma peritonei from the appendix]
1Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
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 (χ2=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.
Insights
The tumor-stroma ratio (TSR) is linked to pseudomyxoma peritonei (PMP) progression and prognosis. A lower TSR (≤10%) is associated with better overall survival in PMP patients treated with CRS and HIPEC.
Area of Science:
- Oncology
- Pathology
- Surgical Oncology
Background:
- Pseudomyxoma peritonei (PMP) is a rare malignancy originating from the appendix.
- Accurate prognostic markers are crucial for managing PMP, a disease characterized by mucinous ascites.
Purpose of the Study:
- To investigate the correlation between the tumor-stroma ratio (TSR) and clinicopathological features, and its impact on disease progression and prognosis in PMP patients.
- To assess the potential of TSR as a novel prognostic indicator for PMP.
Main Methods:
- Retrospective analysis of 30 PMP patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).
- Quantitative assessment of TSR using Image-Pro Plus on hematoxylin-eosin stained pathological images.
- Correlation analysis between TSR and clinicopathological variables, immunohistochemical markers (Ki67, p53, MMR proteins, mucins, cytokeratins), and patient survival.
Main Results:
- TSR was significantly correlated with histopathological type, nerve invasion, Ki67 proliferation index, and p53 mutation status (P<0.05).
- Patients with a lower TSR (≤10%) exhibited a longer median overall survival (19.4 months) compared to those with a higher TSR (>10%) (12.6 months) (P=0.046).
- Overall survival rates at 1, 2, and 3 years were 60.5%, 32.3%, and 27.7%, respectively.
Conclusions:
- The tumor-stroma ratio (TSR) is a significant factor associated with histopathological characteristics, tumor proliferation, and invasion in PMP.
- TSR serves as a valuable and novel prognostic indicator for patients with pseudomyxoma peritonei.

