Toward the molecular dissection of peritoneal pseudomyxoma

Ann Oncol. 2016 Nov;27(11):2097-2103. doi: 10.1093/annonc/mdw314. Epub 2016 Aug 8.


Background: Outcome of pseudomyxoma peritonei (PMP) after cytoreductive surgery (CRS) and hypertermic intraperitoneal chemotherapy (HIPEC) is heterogeneous even after adjusting for clinico-pathological prognostic variables. The identification of additional prognostic or even predictive biomarkers is an unmet clinical need.

Patients and methods: Forty patients with mucinous appendiceal tumors and PMP were clinically eligible and had evaluable tumor samples obtained after CRS and HIPEC. We carried out next-generations sequencing (NGS) of 50 gene's hotspot regions contained in the Hotspot Cancer Panel v2 using the Ion Torrent Personal Genome Machine platform (Life Technologies).

Results: KRAS and GNAS mutations were found in 72% and 52%, and their allelic frequency was below 10% in 55% and 43% of samples, respectively. KRAS and GNAS mutations were associated with worse progression-free survival (PFS) at univariate analysis (P = 0.006 and 0.011, respectively). At multivariate analysis, only KRAS mutations were independently associated with PFS (P = 0.012); GNAS mutations were not-being significantly associated with other poor prognostic features such as incomplete cytoreduction or KRAS mutations. Validation of results was carried out in an independent bi-institutional cohort of 25 patients and the prognostic effect of KRAS mutations was again confirmed in the multivariate model (P = 0.029). NGS approach allowed the discovery of other potentially druggable mutations such as those in PI3K, AKT, LKB1, FGFR3 and PDGFRA.

Conclusions: Given the homogeneity of this series and the sensitivity of NGS in this low-cellularity tumor, we demonstrated for the first time a poor prognostic role of KRAS mutations.

Keywords: GNAS; KRAS; prognosis; pseudomyxoma peritonei.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Chromogranins / genetics*
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Cytoreduction Surgical Procedures
  • Disease-Free Survival
  • Female
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Hyperthermia, Induced
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Pseudomyxoma Peritonei / drug therapy
  • Pseudomyxoma Peritonei / genetics*
  • Pseudomyxoma Peritonei / pathology
  • Pseudomyxoma Peritonei / surgery


  • Biomarkers, Tumor
  • Chromogranins
  • KRAS protein, human
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs
  • Proto-Oncogene Proteins p21(ras)
  • Cisplatin