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Ann Oncol. 2016 Nov;27(11):2097-2103. Epub 2016 Aug 8.

Toward the molecular dissection of peritoneal pseudomyxoma.

Author information

1
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy filippo.pietrantonio@istitutotumori.mi.it.
2
Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.
3
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
4
Department of Surgery, Drexel University College of Medicine, Philadelphia, USA.
5
Oncology Department, University of Milan.
6
Surgery Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.

Abstract

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

PMID:
27502722
DOI:
10.1093/annonc/mdw314
[Indexed for MEDLINE]

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