Establishment of patient derived xenograft model of high-grade mucinous carcinoma peritonei accompanied with signet ring cells and identification of biological characteristics
10.3760/cma.j.issn.0253-3766.2019.12.008
- VernacularTitle: 腹膜高级别黏液癌伴印戒细胞裸小鼠模型的建立及生物学功能鉴定
- Author:
Yulin LIN
1
;
Jue ZHANG
1
;
Zhiran YANG
1
;
Xinbao LI
1
;
Zhonghe JI
1
;
Hongbin XU
2
;
Fengcai YAN
3
;
Quan ZHOU
3
;
Zheng PENG
4
;
Yan LI
1
Author Information
1. Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
2. Department of Myxoma, Aero Space Central Hospital, Beijing 100049, China
3. Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
4. Department of General Surgery, PLA General Hospital, Beijing 100853, China
- Publication Type:Journal Article
- Keywords:
Pseudomyxoma peritonei;
Patient derived xenograft model;
Tumor biology;
Whole-genome exon sequencing;
KIT mutation
- From:
Chinese Journal of Oncology
2019;41(12):923-931
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP.
Methods:PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded.
Results:The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%.
Conclusion:PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.
