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Gastric Cancer
Published in: Gastric Cancer 6/2019

Open Access 01-11-2019 | Gastric Cancer | Original Article

KRAS status is related to histological phenotype in gastric cancer: results from a large multicentre study

Authors: Lindsay C. Hewitt, Yuichi Saito, Tan Wang, Yoko Matsuda, Jan Oosting, Arnaldo N. S. Silva, Hayley L. Slaney, Veerle Melotte, Gordon Hutchins, Patrick Tan, Takaki Yoshikawa, Tomio Arai, Heike I. Grabsch

Published in: Gastric Cancer | Issue 6/2019

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Abstract

Background

Gastric cancer (GC) is histologically a very heterogeneous disease, and the temporal development of different histological phenotypes remains unclear. Recent studies in lung and ovarian cancer suggest that KRAS activation (KRASact) can influence histological phenotype. KRASact likely results from KRAS mutation (KRASmut) or KRAS amplification (KRASamp). The aim of the study was to investigate whether KRASmut and/or KRASamp are related to the histological phenotype in GC.

Methods

Digitized haematoxylin/eosin-stained slides from 1282 GC resection specimens were classified according to Japanese Gastric Cancer Association (JGCA) and the Lauren classification by at least two observers. The relationship between KRAS status, predominant histological phenotype and clinicopathological variables was assessed.

Results

KRASmut and KRASamp were found in 68 (5%) and 47 (7%) GCs, respectively. Within the KRASmut and KRASamp cases, the most frequent GC histological phenotype was moderately differentiated tubular 2 (tub2) type (KRASmut: n = 27, 40%; KRASamp: n = 21, 46%) or intestinal type (KRASmut: n = 41, 61%; KRASamp: n = 23, 50%). Comparing individual histological subtypes, mucinous carcinoma displayed the highest frequency of KRASmut (JGCA: n = 6, 12%, p = 0.012; Lauren: n = 6, 12%, p = 0.013), and KRASamp was more frequently found in poorly differentiated solid type (n = 12, 10%, p = 0.267) or indeterminate type (n = 12, 10%, p = 0.480) GC. 724 GCs (57%) had intratumour morphological heterogeneity.

Conclusions

This is the largest GC study investigating KRAS status and histological phenotype. We identified a relationship between KRASmut and mucinous phenotype. The high level of intratumour morphological heterogeneity could reflect KRASmut heterogeneity, which may explain the failure of anti-EGFR therapy in GC.
Appendix
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Metadata
Title
KRAS status is related to histological phenotype in gastric cancer: results from a large multicentre study
Authors
Lindsay C. Hewitt
Yuichi Saito
Tan Wang
Yoko Matsuda
Jan Oosting
Arnaldo N. S. Silva
Hayley L. Slaney
Veerle Melotte
Gordon Hutchins
Patrick Tan
Takaki Yoshikawa
Tomio Arai
Heike I. Grabsch
Publication date
01-11-2019
Publisher
Springer Singapore
Published in
Gastric Cancer / Issue 6/2019
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-019-00972-6

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