PMID- 37151285 OWN - NLM STAT- MEDLINE DCOM- 20230509 LR - 20230517 IS - 2167-8359 (Electronic) IS - 2167-8359 (Linking) VI - 11 DP - 2023 TI - Somatic mutation profiling, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein expression in HER2-amplified colorectal cancer. PG - e15261 LID - 10.7717/peerj.15261 [doi] LID - e15261 AB - 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. CI - (c)2023 Liu et al. FAU - Liu, Xiao-Ting AU - Liu XT AD - Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Kou, Zhi-Yong AU - Kou ZY AD - Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Zhang, Hushan AU - Zhang H AD - Zhaotong Healthy Vocational College, Zhaotong, Yunnan, China. FAU - Dong, Jian AU - Dong J AD - Colorectal Cancer Clinical Research Center, Yunnan Cancer Hospital, Kunming, Yunnan, China. FAU - Zhang, Jian-Hua AU - Zhang JH AD - Department of General Surgery, The Third People's Hospital of Honghe Prefecture, Honghe, Yunnan, China. FAU - Peng, You-Jun AU - Peng YJ AD - Department of General Surgery, The Third People's Hospital of Honghe Prefecture, Honghe, Yunnan, China. FAU - Ma, Shu Min AU - Ma SM AD - Department of General Surgery, The Second People's Hospital of Qujing, Qujing, Yunnan, China. FAU - Liang, Lei AU - Liang L AD - Department of General Surgery, The Third People's Hospital of Honghe Prefecture, Honghe, Yunnan, China. FAU - Meng, Xuan-Yu AU - Meng XY AD - Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Zhou, Yuan AU - Zhou Y AD - Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Yang, Jun AU - Yang J AD - Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230502 PL - United States TA - PeerJ JT - PeerJ JID - 101603425 RN - EC 2.7.10.1 (ERBB2 protein, human) RN - 0 (B7-H1 Antigen) SB - IM MH - Humans MH - B7-H1 Antigen/genetics MH - In Situ Hybridization, Fluorescence MH - *Tertiary Lymphoid Structures/genetics MH - *Colorectal Neoplasms/genetics MH - Mutation MH - Tumor Microenvironment PMC - PMC10162038 OTO - NOTNLM OT - PD-L1 expression OT - Colorectal cancer OT - HER2 OT - Somatic mutation profiling OT - Tumour immune microenvironment COIS- The authors declare there are no competing interests. EDAT- 2023/05/08 06:42 MHDA- 2023/05/09 10:16 PMCR- 2023/05/02 CRDT- 2023/05/08 03:47 PHST- 2023/01/12 00:00 [received] PHST- 2023/03/28 00:00 [accepted] PHST- 2023/05/09 10:16 [medline] PHST- 2023/05/08 06:42 [pubmed] PHST- 2023/05/08 03:47 [entrez] PHST- 2023/05/02 00:00 [pmc-release] AID - 15261 [pii] AID - 10.7717/peerj.15261 [doi] PST - epublish SO - PeerJ. 2023 May 2;11:e15261. doi: 10.7717/peerj.15261. eCollection 2023.