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Updated: Apr 23, 2026
Culture and Imaging of Ex Vivo Organotypic Pseudomyxoma Peritonei Tumor Slices from Resected Human Tumor Specimens
Published on: December 9, 2022
Genomic profile of pseudomyxoma peritonei analyzed using next-generation sequencing and immunohistochemistry
Pirjo Nummela1, Lilli Saarinen, Alexandra Thiel
1Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
Abstract:
Pseudomyxoma peritonei (PMP) is a relatively rare clinical syndrome characterized by neoplastic epithelial cells growing in the peritoneal cavity and secreting mucinous ascites. Our aim was to explore the molecular events behind this fatal but under-investigated disease. We extracted DNA from 19 appendix-derived PMP tumors and nine corresponding normal tissues, and analyzed the mutational hotspot areas of 48 cancer-related genes by amplicon-based next-generation sequencing (NGS). Further, we analyzed the protein expression of V600E mutated BRAF, MLH1, MSH2, MSH6 and p53 from a larger set of PMP tumors (n = 74) using immunohistochemistry. With NGS, we detected activating somatic KRAS mutations in all of the tumors studied. GNAS was mutated in 63% of the tumors with no marked difference between low-grade and high-grade tumors. Only one (5.3%) tumor showed oncogenic PIK3CA mutation, one showed oncogenic AKT1 mutation, three (15.8%) showed SMAD4 mutations and none showed an APC mutation. P53 protein was aberrantly expressed in higher proportion of high-grade tumors as compared with low-grade ones (31.3 vs. 7.1%, respectively; p = 0.012) and aberrant expression was an independent factor for reduced overall survival (p = 0.002). BRAF V600E mutation was only found in one (1.4%) high-grade tumor by immunohistochemistry (n = 74). All the studied tumors expressed mismatch repair proteins MLH1, MSH2 and MSH6. Our results indicate that KRAS mutations are evident in all and GNAS mutations in most of the PMPs, but BRAF V600E, PIK3CA and APC mutations are rare. Aberrantly expressed p53 is associated with high-grade histology and reduced survival.
Insights
Activating KRAS mutations are found in all pseudomyxoma peritonei (PMP) tumors, and GNAS mutations are common. Aberrant p53 expression correlates with high-grade PMP and poorer survival, indicating potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pseudomyxoma peritonei (PMP) is a rare malignancy characterized by mucinous ascites and epithelial cell growth within the peritoneal cavity.
- The molecular underpinnings of PMP remain under-investigated, hindering the development of targeted therapies.
Purpose of the Study:
- To elucidate the molecular landscape of pseudomyxoma peritonei.
- To identify genetic alterations and protein expression patterns associated with PMP progression and patient survival.
Main Methods:
- DNA extraction from 19 appendix-derived PMP tumors and matched normal tissues.
- Next-generation sequencing (NGS) of 48 cancer-related genes to identify mutations.
- Immunohistochemistry analysis of BRAF V600E, MLH1, MSH2, MSH6, and p53 protein expression in 74 PMP tumors.
Main Results:
- Activating somatic KRAS mutations were detected in all PMP tumors analyzed by NGS.
- GNAS mutations were present in 63% of tumors; PIK3CA, AKT1, SMAD4, and APC mutations were rare.
- Aberrant p53 protein expression was significantly higher in high-grade PMP (31.3%) compared to low-grade (7.1%) and was an independent predictor of reduced survival (p=0.002).
- BRAF V600E mutation was found in only one tumor (1.4%).
- All tumors expressed mismatch repair proteins MLH1, MSH2, and MSH6.
Conclusions:
- KRAS mutations are a near-universal event in PMP, and GNAS mutations are frequent.
- Aberrant p53 expression is linked to aggressive PMP histology and unfavorable prognosis.
- These findings highlight key molecular drivers in PMP and identify p53 as a potential prognostic biomarker.
