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Somatic mutation profiling, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein expression in HER2-amplified colorectal cancer

Authors :
Xiao-Ting Liu
Zhi-Yong Kou
Hushan Zhang
Jian Dong
Jian-Hua Zhang
You-Jun Peng
Shu Min Ma
Lei Liang
Xuan-Yu Meng
Yuan Zhou
Jun Yang
Source :
PeerJ, Vol 11, p e15261 (2023)
Publication Year :
2023
Publisher :
PeerJ Inc., 2023.

Abstract

The status of human epidermal growth factor receptor 2 (HER2) for the prognosis in colorectal cancer (CRC) is controversial, and the characteristics of the somatic mutation spectrum, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein are unknown in HER2-amplified colorectal cancer (HACC). In order to explore these characteristics along with their correlation with clinicopathological factors and prognosis in HACC. Samples of 812 CRC patients was collected. After immunohistochemistry (IHC), 59 of 812 were found to be HER2-positive, then 26 of 59 samples were further determined to be HER2 amplification by fluorescence in situ hybridization (FISH). Somatic mutation profiling of HACC was analysed using whole exome sequencing (WES). Multiplex fluorescence immunohistochemistry (mIHC) was used for tumor-infiltrating leukocytes and tertiary lymphoid structures (TLSs), while PD-L1 protein was detected by IHC. Our results indicate that the detection rates of HER2 positivity by IHC and FISH were 7.3% and 3.2% respectively, and HER2 amplification is correlated with distant tumour metastasis. The somatic mutation profiling revealed no differences between HACC and HER2-negative CRC. However, TP 53 strongly correlated with poor prognosis in HACC. Furthermore, tumor-infiltrating T cells and TLSs in the tumor immune microenvironment, as well as PD-L1 expression, were higher in HACC than in HER2-negative controls. However, none of them were associated with the prognosis of HACC. In all, HER2 amplification is correlated with distant metastasis and TP53 gene mutation may be a potential protective mechanism of HACC.

Details

Language :
English
ISSN :
21678359
Volume :
11
Database :
Directory of Open Access Journals
Journal :
PeerJ
Publication Type :
Academic Journal
Accession number :
edsdoj.f8099acb048541078da28263dbf7714a
Document Type :
article
Full Text :
https://doi.org/10.7717/peerj.15261