Targeted Next-Generation Sequencing Improves the Prognostication of Patients with Disseminated Appendiceal Mucinous Neoplasms (Pseudomyxoma Peritonei).

Autor: Wald AI; Department of Pathology, UPMC Presbyterian Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Pingpank JF; Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Ongchin M; Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Hall LB; Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Jones H; Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Altpeter S; Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Liebdzinski M; Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Hamed AB; Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Derby J; Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Nikiforova MN; Department of Pathology, UPMC Presbyterian Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Bell PD; Department of Pathology, UPMC Presbyterian Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Paniccia A; Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Zureikat AH; Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Gorantla VC; Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Rhee JC; Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Thomas R; Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Bartlett DL; AHN Cancer Institute, Allegheny Health Network, Pittsburgh, PA, USA., Smith K; Department of Pathology, UPMC Presbyterian Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Henn P; Department of Pathology, University of Colorado Hospital, Aurora, CO, USA., Theisen BK; Department of Pathology, Henry Ford Health System, Detroit, MI, USA., Shyu S; Department of Pathology, WellSpan York Hospital, York, PA, USA., Shalaby A; Department of Pathology, UPMC Presbyterian Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Choudry MHA; Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. choudrymh@upmc.edu., Singhi AD; Department of Pathology, UPMC Presbyterian Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. singhiad@upmc.edu.
Jazyk: angličtina
Zdroj: Annals of surgical oncology [Ann Surg Oncol] 2023 Nov; Vol. 30 (12), pp. 7517-7526. Date of Electronic Publication: 2023 Jun 14.
DOI: 10.1245/s10434-023-13721-y
Abstrakt: Background: Appendiceal mucinous neoplasms (AMNs) with disseminated disease (pseudomyxoma peritonei) are heterogeneous tumors with variable clinicopathologic behavior. Despite the development of prognostic systems, objective biomarkers are needed to stratify patients. With the advent of next-generation sequencing (NGS), it remains unclear if molecular testing can improve the evaluation of disseminated AMN patients.
Methods: Targeted NGS was performed for 183 patients and correlated with clinicopathologic features to include American Joint Committee on Cancer/World Health Organization (AJCC/WHO) histologic grade, peritoneal cancer index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS).
Results: Genomic alterations were identified for 179 (98%) disseminated AMNs. Excluding mitogen-activated protein kinase genes and GNAS due to their ubiquitous nature, collective genomic alterations in TP53, SMAD4, CDKN2A, and the mTOR genes were associated with older mean age, higher AJCC/WHO histologic grade, lymphovascular invasion, perineural invasion, regional lymph node metastasis, and lower mean PCI (p < 0.040). Patients harboring TP53, SMAD4, ATM, CDKN2A, and/or mTOR gene alterations were found to have lower OS rates of 55% at 5 years and 14% at 10 years, compared with 88% at 5 years and 88% at 10 years for patients without the aforementioned alterations (p < 0.001). Based on univariate and multivariate analyses, genomic alterations in TP53, SMAD4, ATM, CDKN2A, and/or the mTOR genes in disseminated AMNs were a negative prognostic factor for OS and independent of AJCC/WHO histologic grade, PCI, CC score, and hyperthermic intraperitoneal chemotherapy treatment (p = 0.006).
Conclusions: Targeted NGS improves the prognostic assessment of patients with disseminated AMNs and identifies patients who may require increased surveillance and/or aggressive management.
(© 2023. Society of Surgical Oncology.)
Databáze: MEDLINE
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