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Amplification of KRAS and its heterogeneity in non-Asian gastric adenocarcinomas

Jan Rehkaemper1, Michael Korenkov2, Alexander Quaas3

  • 1Institute of Pathology, University Hospital Cologne, Cologne, Germany. jan.rehkaemper@uk-koeln.de.

BMC Cancer
|June 24, 2020
PubMed
Abstract

Insights

KRAS amplification in gastric cancer is linked to a worse prognosis, particularly in patients not receiving neoadjuvant therapy. This amplification, found in 5.7% of tumors, shows heterogeneity and may indicate a more aggressive cancer subgroup.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Gastric cancer is a leading cause of cancer mortality globally.
  • Curative options are limited to early-stage disease; advanced stages require novel therapeutic targets.
  • KRAS amplification is an emerging target, but its prognostic relevance in non-Asian gastric adenocarcinomas is unclear.

Purpose of the Study:

  • To investigate the prevalence and prognostic significance of KRAS amplification in gastric adenocarcinomas.
  • To analyze the distribution and correlation with protein expression of KRAS amplification.
  • To explore the association with tumor characteristics and clinical outcomes in a non-Asian cohort.

Main Methods:

  • Analyzed KRAS amplification and protein expression in 582 gastric adenocarcinomas using FISH and immunohistochemistry.
  • Correlated amplification status with clinico-pathological features, clinical outcome, and TCGA molecular subtypes.
  • Assessed overall survival in relation to KRAS amplification status, stratified by neoadjuvant treatment.

Main Results:

  • KRAS amplification was detected in 5.7% (27/470) of tumors and correlated with KRAS protein expression.
  • Intratumoral heterogeneity of KRAS amplification was observed in 51.9% of amplified tumors.
  • A worse outcome was associated with KRAS amplification in patients without neoadjuvant pre-treatment, but not in the overall cohort.

Conclusions:

  • KRAS amplification confers an unfavorable prognosis in gastric cancer patients without neoadjuvant therapy, consistent with findings in Asian cohorts.
  • Intratumoral heterogeneity of KRAS amplification may indicate a more aggressive tumor population, often seen with lymph node metastases.
  • Gastric adenocarcinomas with KRAS amplification represent a therapeutically relevant subgroup, even with heterogeneous distribution.
Keywords:
Fluorescence-in-situ-hybridization (FISH)Gastric adenocarcinomaHeterogeneityKRAS amplificationPrognosis

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