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.
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http://dx.doi.org/10.1002/ijc.29245 | DOI Listing |
Front Oncol
January 2025
Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, Dallas, TX, United States.
Introduction: Low grade appendiceal mucinous neoplasms (LAMN) are indolent tumors that lack invasive potential but may present as pseudomyxoma peritonei. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) significantly improves both overall and recurrence free survival. While systemic chemotherapy is generally considered ineffective for LAMN, little literature is available to support this notion.
View Article and Find Full Text PDFSurg Pract Sci
September 2024
Department of General Surgery, Joondalup Health Campus, Perth, Western Australia, Corner Grant Boulevard & Shenton Avenue, Joondalup, Western Australia, Australia, 6027.
Introduction: Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) represent a high-risk for venous thromboembolism (VTE) due to malignancy, prolonged surgery and immobility. We investigated the incidence of and risk factors for VTE following CRS/IPC.
Materials And Methods: Data was analysed on 130 CRS/IPC performed over a 6-year period at a single centre, the Western Australian Peritonectomy Service (WAPS), on lower gastrointestinal neoplasia: pseudomyxoma peritoneii (PMP), colorectal cancer (CRC) and appendix cancer (AC).
Ann Surg Oncol
January 2025
Department of Surgical Sciences, Colorectal Surgery, Uppsala University, Uppsala, Sweden.
Background: Prediction of open-close and long-term outcome is challenging in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prognostic scores often include factors not known at baseline. Therefore, we aimed to analyze whether patterns of preoperative tumor markers could aid in prediction of open-close surgery and outcome in patients with pseudomyxoma peritonei (PMP) or colorectal peritoneal metastases (PM).
View Article and Find Full Text PDFAppl Immunohistochem Mol Morphol
January 2025
Department of Pathology.
Histologic grade is a key predictor for pseudomyxoma peritonei (PMP) of appendiceal origin that is used to guide clinical management. However, some tumors demonstrate disease behavior that deviates from their histologic grade. A recent study suggested that TP53, GNAS, and RAS mutation analysis could stratify tumors into distinct molecular groups with different prognosis.
View Article and Find Full Text PDFCureus
December 2024
Department of Surgery, Kitakyushu City Yahata Hospital, Kitakyushu, JPN.
A low-grade appendiceal mucinous neoplasm (LAMN) is a rare condition, occurring in 0.08-4.1% of appendectomy cases.
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