Journal article
Appendix-derived Pseudomyxoma Peritonei (PMP) Molecular Profiling Toward Treatment of a Rare Malignancy
American journal of clinical oncology, v 41(8), pp 777-783
01 Aug 2018
PMID: 28263231
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Objectives: Pseudomyxoma peritonei (PMP) is a rare malignancy originating from the appendix, characterized by disseminated mucinous tumor implants on peritoneal surfaces. We examined the role of multiplatform molecular profiling to study biomarker-guided treatment strategies for this rare malignancy.
Methods: A total of 54 patients with appendix-derived PMP were included in the study. Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing), protein expression (immunohistochemistry), and gene amplification (C/fluorescent in situ hybridization).
Results: Targeted sequencing of 47 genes detected variants in KRAS (81%), GNAS (74%), SMAD4 (16%), and ATM (16%). Mutations were found at low frequencies (n =1 to 2) in APC, BRAF, PIK3CA, MLH1, and TP53. GNAS and KRAS co-occurrence was found in 87%. Protein overexpression was found in epidermal growth factor receptor (83%), cyclooxygenase-2 (73%), cMET (63%), cKIT (58%), and platelet-derived growth factor receptor alpha (58%). Immune checkpoint expression was found in 36% (programmed cell death protein 1) and 18% (programmed death-ligand 1). Surrogate markers of cell proliferation were found at low rates (TLE3 23%, TOP2A 22%), consistent with the slow-growing biology of PMP. Phosophatase and tensin homolog was intact (wild type [ 100%]) and positive (immunohistochemistry [ 80%]). Patients exhibited stable microsatellite status and mismatch repair proficiency (93%). Importantly, multidrug resistance protein expression was elevated (100% BCRP, 94% MRP1, 88% PGP). Markers for gemcitabine (RRM1), fluorouracil (TS), oxaliplatin (ERCC1), and irinotecan (TOPO1) chemosensitivities were detected at favorable rates: 93%, 87%, 77% and 65%, respectively.
Conclusions: Molecular profiling by multiple platforms identified potential therapies for the nontargetable KRAS-mutated population. The role of cMET-targeted therapeutics and immune checkpoint inhibitors merits further investigation. Biomarker-guided selection of cytotoxic chemotherapies may facilitate efficacy to systemic treatment.
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Details
- Title
- Appendix-derived Pseudomyxoma Peritonei (PMP) Molecular Profiling Toward Treatment of a Rare Malignancy
- Creators
- Elizabeth M. Gleeson - Drexel UniversityRebecca Feldman - Carolinas Healthcare SystemBeth L. Mapow - Drexel UniversityLynn T. Mackovick - Drexel UniversityKristine M. Ward - Drexel UniversityWilliam F. Morano - Drexel UniversityRene R. Rubin - Drexel UniversityWilbur B. Bowne - Drexel University
- Publication Details
- American journal of clinical oncology, v 41(8), pp 777-783
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 7
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Web of Science ID
- WOS:000453919800009
- Scopus ID
- 2-s2.0-85014549308
- Other Identifier
- 991019168115404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology