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Pathology & Oncology Research

, Volume 25, Issue 1, pp 333–340 | Cite as

KRAS Mutation in Gastric Cancer and Prognostication Associated with Microsatellite Instability Status

  • Karol PolomEmail author
  • Kakoli Das
  • Daniele Marrelli
  • Giandomenico Roviello
  • Valeria Pascale
  • Costantino Voglino
  • Henry Rho
  • Patrick Tan
  • Franco Roviello
Original Article

Abstract

Microsatellite instability (MSI) is one of the subgroups based on the new molecular classification of gastric cancer (GC). In this study, we analyzed the role of KRAS status in MSI GC and the impact of MSI status on KRAS mutation. We performed analysis on 595 GC patients. Polymerase chain reaction (PCR) was used for the screening of KRAS mutation (exon 2) and 5 quasi-monomorphic mononucleotide repeats, namely, BAT-26, BAT-25, NR -24, NR-21, and NR-27 were used to determine the MSI status. The KRAS and MSI status were then compared with clinicopathologic data of the GC patients. MSI GC was found in 20.3% of all cases. KRAS mutation was seen in 24 patients; 18 were MSI (75%) and 6 were microsatellite stable (MSS) (25%). MSI GC patients with KRAS mutation were older and mostly female, but MSS presented more advanced T and N stage of the disease, more cardia tumors, and adjuvant treatment. Five-year survival was 72.2% for KRAS mutation patients with MSI and 0% for MSS (p < 0.001). Although KRAS mutations in GC are linked with MSI in the majority of cases, KRAS mutations with MSS status presented with a poor prognosis and a worse outcome. In multivariate analysis, MSI was associated with better survival (p < 0.001) but KRAS was with worse survival (p = 0.304). Our study suggests that KRAS mutations are based on MSI status rather than different codon subtypes of mutation, and such a division could be used to determine the GC patient outcome.

Keywords

Stomach cancer KRAS mutation Mismatch repair deficiency Molecular Prognosis 

Notes

Acknowledgements

None.

Funding

This work was supported by:

Istituto Toscano Tumori (ITT) grant entitled Gene expression profiles and therapy of gastric cancer- (Grant No. ITT-2007).

European Union’s Seventh Framework Programme (FP7), GastricGlycoExplorer under grant agreement n° [316929] (Karol Polom, Franco Roviello).

Compliance with Ethical Standards

Conflict of Interest

The authors declare they have no conflict of interest.

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study.

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Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  • Karol Polom
    • 1
    • 2
    Email author return OK on get
  • Kakoli Das
    • 3
  • Daniele Marrelli
    • 1
  • Giandomenico Roviello
    • 4
    • 5
  • Valeria Pascale
    • 1
  • Costantino Voglino
    • 1
  • Henry Rho
    • 6
  • Patrick Tan
    • 3
    • 7
    • 8
    • 9
  • Franco Roviello
    • 1
  1. 1.General Surgery and Surgical Oncology DepartmentUniversity of SienaSienaItaly
  2. 2.Department of Surgical OncologyMedical University of GdanskGdanskPoland
  3. 3.Cancer and Stem Cell Biology ProgrammeDuke-NUS Medical SchoolSingaporeSingapore
  4. 4.Medical Oncology Unit, Department of OncologySan Donato HospitalArezzoItaly
  5. 5.Department of Medical, Surgery and Health SciencesUniversity of TriesteTriesteItaly
  6. 6.University of Medical Sciences PoznanPoznanPoland
  7. 7.SingHealth/Duke-NUS Institute of Precision MedicineNational Heart CentreSingaporeSingapore
  8. 8.Cancer Science Institute of SingaporeNational University of SingaporeSingaporeSingapore
  9. 9.Cellular and Molecular ResearchNational Cancer CentreSingaporeSingapore

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