PMID- 31865178
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1936-5233 (Print)
IS  - 1936-5233 (Electronic)
IS  - 1936-5233 (Linking)
VI  - 13
IP  - 2
DP  - 2020 Feb
TI  - PIK3CA and KRAS Amplification in Esophageal Adenocarcinoma and their Impact on 
      the Inflammatory Tumor Microenvironment and Prognosis.
PG  - 157-164
LID - S1936-5233(19)30274-8 [pii]
LID - 10.1016/j.tranon.2019.10.013 [doi]
AB  - Gene amplifications of PIK3CA or KRAS induce a downstream activation of the 
      AKT-mTOR or RAF-ERK-pathways. Interactions of the active AKT pathway have been 
      implicated in the inflammatory tumor microenvironment. Nothing is known about 
      these interactions or prognostic power in esophageal adenocarcinoma (EAC). We 
      retrospectively analyzed a large cohort of 685 EAC considering KRAS and PIK3CA 
      gene amplification using fluorescence in situ hybridization (FISH) and 
      immunohistochemistry. These results were correlated with clinical and molecular 
      data as well as the inflammatory tumor microenvironment. Amplifications of KRAS 
      were seen in 94 patients (17.1%), PIK3CA amplifications in 23 patients (5.0%). 
      KRAS amplifications significantly correlated with nodal positive patients and 
      poorer overall survival (OS) in the subgroup without neoadjuvant treatment 
      (p = 0.004), coamplifications of Her2 (p = 0.027), and TP53 mutations 
      (p = 0.016). PIK3CA amplifications significantly correlated with a high amount of 
      tumor infiltrating T cells (p = 0.003) and showed a tendency to better OS 
      (p = 0.068). A correlation with checkpoint makers (PD-L1, LAG3, VISTA, TIM3, IDO) 
      could not be revealed. Our findings are the first to link the KRAS amplified 
      genotype with lymphonodal positivity and poor prognosis and the PIK3CA-amplified 
      genotype with a T cell-rich microenvironment in EAC. Future studies must show 
      whether these two genotype subgroups can be therapeutically influenced. A dual 
      inhibition of MEK and SHP2T could be effective in the subgroup of KRAS amplified 
      EACs and an immune checkpoint blockade may prove to be particularly promising in 
      the subgroup of PIK3CA-amplified EACs.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Essakly, Ahlem
AU  - Essakly A
AD  - Institute of Pathology, University Hospital Cologne, Germany.
FAU - Loeser, Heike
AU  - Loeser H
AD  - Institute of Pathology, University Hospital Cologne, Germany. Electronic address: 
      heike.loeser@uk-koeln.de.
FAU - Kraemer, Max
AU  - Kraemer M
AD  - Institute of Pathology, University Hospital Cologne, Germany.
FAU - Alakus, Hakan
AU  - Alakus H
AD  - Department of General, Visceral and Cancer Surgery, University Hospital Cologne, 
      Germany.
FAU - Chon, Seung-Hun
AU  - Chon SH
AD  - Department of General, Visceral and Cancer Surgery, University Hospital Cologne, 
      Germany.
FAU - Zander, Thomas
AU  - Zander T
AD  - Department of Internal Medicine I, University Hospital Cologne, Germany.
FAU - Buettner, Reinhard
AU  - Buettner R
AD  - Institute of Pathology, University Hospital Cologne, Germany.
FAU - Hillmer, Axel M
AU  - Hillmer AM
AD  - Institute of Pathology, University Hospital Cologne, Germany.
FAU - Bruns, Christiane J
AU  - Bruns CJ
AD  - Department of General, Visceral and Cancer Surgery, University Hospital Cologne, 
      Germany.
FAU - Schroeder, Wolfgang
AU  - Schroeder W
AD  - Department of General, Visceral and Cancer Surgery, University Hospital Cologne, 
      Germany.
FAU - Gebauer, Florian
AU  - Gebauer F
AD  - Department of General, Visceral and Cancer Surgery, University Hospital Cologne, 
      Germany.
FAU - Quaas, Alexander
AU  - Quaas A
AD  - Institute of Pathology, University Hospital Cologne, Germany.
LA  - eng
PT  - Journal Article
DEP - 20191219
PL  - United States
TA  - Transl Oncol
JT  - Translational oncology
JID - 101472619
PMC - PMC6931191
EDAT- 2019/12/23 06:00
MHDA- 2019/12/23 06:01
PMCR- 2019/12/19
CRDT- 2019/12/23 06:00
PHST- 2019/06/12 00:00 [received]
PHST- 2019/10/22 00:00 [revised]
PHST- 2019/10/25 00:00 [accepted]
PHST- 2019/12/23 06:00 [pubmed]
PHST- 2019/12/23 06:01 [medline]
PHST- 2019/12/23 06:00 [entrez]
PHST- 2019/12/19 00:00 [pmc-release]
AID - S1936-5233(19)30274-8 [pii]
AID - 10.1016/j.tranon.2019.10.013 [doi]
PST - ppublish
SO  - Transl Oncol. 2020 Feb;13(2):157-164. doi: 10.1016/j.tranon.2019.10.013. Epub 
      2019 Dec 19.