PMID- 33384243
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20211214
IS  - 1938-0674 (Electronic)
IS  - 1533-0028 (Linking)
VI  - 20
IP  - 2
DP  - 2021 Jun
TI  - Prognostic Value and Molecular Landscape of HER2 Low-Expressing Metastatic 
      Colorectal Cancer.
PG  - 113-120.e1
LID - S1533-0028(20)30156-0 [pii]
LID - 10.1016/j.clcc.2020.11.002 [doi]
AB  - BACKGROUND: The prognostic value and molecular landscape of human epidermal 
      growth factor receptor 2 (HER2) low-expressing (HER2-L) metastatic colorectal 
      cancer (mCRC) remain unclear. PATIENTS AND METHODS: This study enrolled patients 
      with mCRC who had undergone surgical resection of primary tumor. Using the 
      specimen, we evaluated HER2 expression by immunohistochemistry (IHC) and 
      fluorescence in situ hybridization (FISH). HER2 positivity was defined as 
      follows: HER2 positivity (HER2-Pos) as IHC 3 + or IHC 2+/FISH positive, HER2-L as 
      IHC 2+/FISH negative or IHC 1+, and HER2 negativity (HER2-Neg) as IHC 0+. Gene 
      alterations were determined by next-generation sequencing. RESULTS: Between 2005 
      and 2015, a total of 370 patients were analyzed, comprising 15 patients (4%) with 
      HER2-Pos, 21 (6%) with HER2-L, and 334 (90%) with HER2-Neg disease. The 
      clinicopathologic characteristics among groups had no differences. HER2-L had a 
      significantly higher proportion of coaltered RAS mutation than HER2-Pos (P = 
      .037). With a median follow-up of 101.8 months, HER2-L had a significantly better 
      median overall survival than HER2-Pos (P = .029) (18.2 months in HER2-Pos vs. 
      33.3 in HER2-L vs. 27.9 in HER2-Neg). In 58 patients harboring wild-type RAS and 
      receiving anti-EGFR antibody therapy, HER2-L had a better median progression-free 
      survival tendency than HER2-Pos, with 2.2 months in HER2-Pos, 7.8 in HER2-L, and 
      5.1 in HER2-Neg (P = .036). CONCLUSION: HER2-L mCRC showed a better prognosis 
      than HER2-Pos mCRC, and it is similar to HER2-Neg mCRC. Hence, HER2-L mCRC might 
      have different biologic behavior in terms of prognostic value and molecular 
      landscape of mCRC, suggesting the possibility of implementation of HER2-guided 
      clinical development against HER2-expressing mCRC.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Yagisawa, Masataka
AU  - Yagisawa M
AD  - Department of Gastroenterology and Gastrointestinal Oncology, National Cancer 
      Center Hospital East, Kashiwa, Chiba, Japan; Department of Medical Oncology, 
      Japanese Red Cross Kitami Hospital, Kitami, Hokkaido, Japan.
FAU - Sawada, Kentaro
AU  - Sawada K
AD  - Department of Medical Oncology, Kushiro Rosai Hospital, Kushiro, Hokkaido, Japan.
FAU - Nakamura, Yoshiaki
AU  - Nakamura Y
AD  - Department of Gastroenterology and Gastrointestinal Oncology, National Cancer 
      Center Hospital East, Kashiwa, Chiba, Japan.
FAU - Fujii, Satoshi
AU  - Fujii S
AD  - Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, 
      National Cancer Center, Kashiwa, Chiba, Japan; Department of Molecular Pathology, 
      Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.
FAU - Yuki, Satoshi
AU  - Yuki S
AD  - Department of Gastroenterology and Hepatology, Hokkaido University Hospital, 
      Sapporo, Hokkaido, Japan.
FAU - Komatsu, Yoshito
AU  - Komatsu Y
AD  - Cancer Center, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.
FAU - Yoshino, Takayuki
AU  - Yoshino T
AD  - Department of Gastroenterology and Gastrointestinal Oncology, National Cancer 
      Center Hospital East, Kashiwa, Chiba, Japan.
FAU - Sakamoto, Naoya
AU  - Sakamoto N
AD  - Department of Gastroenterology and Hepatology, Hokkaido University Hospital, 
      Sapporo, Hokkaido, Japan.
FAU - Taniguchi, Hiroya
AU  - Taniguchi H
AD  - Department of Gastroenterology and Gastrointestinal Oncology, National Cancer 
      Center Hospital East, Kashiwa, Chiba, Japan. Electronic address: 
      hirtanig@east.ncc.go.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201113
PL  - United States
TA  - Clin Colorectal Cancer
JT  - Clinical colorectal cancer
JID - 101120693
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/*metabolism
MH  - Colorectal Neoplasms/*metabolism/*pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Progression-Free Survival
MH  - Receptor, ErbB-2/*metabolism
OTO - NOTNLM
OT  - Colorectal cancer
OT  - HER2 low-expressing
OT  - Heterogeneity
OT  - Prognosis
OT  - RAS mutation
EDAT- 2021/01/02 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/01/01 05:16
PHST- 2020/08/24 00:00 [received]
PHST- 2020/10/23 00:00 [revised]
PHST- 2020/11/08 00:00 [accepted]
PHST- 2021/01/02 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/01/01 05:16 [entrez]
AID - S1533-0028(20)30156-0 [pii]
AID - 10.1016/j.clcc.2020.11.002 [doi]
PST - ppublish
SO  - Clin Colorectal Cancer. 2021 Jun;20(2):113-120.e1. doi: 
      10.1016/j.clcc.2020.11.002. Epub 2020 Nov 13.