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

PeerJ

article

Xiao-Ting Liu¹  Zhi-Yong Kou¹  Hushan Zhang²  Jian Dong³  Jian-Hua Zhang⁴  You-Jun Peng⁴  Shu Min Ma⁵  Lei Liang⁴  Xuan-Yu Meng¹  Yuan Zhou¹  Jun Yang¹ 

[1] Department of Oncology, The First Affiliated Hospital of Kunming Medical University;Zhaotong Healthy Vocational College;Colorectal Cancer Clinical Research Center, Yunnan Cancer Hospital;Department of General Surgery, The Third People’s Hospital of Honghe Prefecture;Department of General Surgery, The Second People’s Hospital of Qujing

关键词: Colorectal cancer;    HER2;    Tumour immune microenvironment;    PD-L1 expression;    Somatic mutation profiling;   

DOI  :  10.7717/peerj.15261

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

CC BY