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- Title
Molecular Typing and Clinical Characteristics of Synchronous Multiple Primary Colorectal Cancer.
- Authors
Zhao, Yandong; Wu, Jingjing; Pei, Fengyun; Zhang, Yanxiang; Bai, Shaomei; Shi, Lishuo; Zhang, Xiang; Ma, Jingjiao; Zhao, Ximeng; Ma, Tonghui; Wang, Jianping; Huang, Meijin; Fan, Xinjuan; Huang, Jun
- Abstract
Key Points: Question: What are the molecular characteristics and clinical features of synchronous multiple primary colorectal cancer (sMPCC)? Findings: This cohort study of 239 patients with sMPCC found that the deficient mismatch repair (dMMR)/microsatellite instability–high (MSI-H) frequencies in sMPCC were significantly higher than those in single primary colorectal cancer. The MMR/MSI status of each lesion might be different in sMPCC and can be classified into 3 subgroups: all dMMR/MSI-H, dMMR/MSI-H and proficient MMR (pMMR)/microsatellite stability (MSS), and all pMMR/MSS. Meaning: These findings suggest that sMPCC can be classified into subgroups according to the MMR/MSI status of each lesion, which might be applied to guide personalized therapies for better disease management. This cohort study evaluates the molecular characteristics and clinical features of synchronous multiple primary colorectal cancer. Importance: Synchronous multiple primary colorectal cancer (sMPCC) is clinically rare, but its incidence has increased over the past decade. However, little is known about the molecular and clinical features of sMPCC, which may differ from those of single primary colorectal cancer (SPCRC). Objective: To evaluate the clinical characteristics and pathogenic variations in lesions and the molecular typing of sMPCC. Design, Setting, and Participants: From November 2012 to April 2021, patients with colorectal cancer (CRC) treated at the Sixth Affiliated Hospital of Sun Yat-sen University were enrolled in this cohort study. Follow-up ended on January 31, 2022. Main Outcomes and Measures: The primary outcome was mismatch repair (MMR) status of each lesion in all patients examined using immunohistochemistry (IHC). Microsatellite instability (MSI) and tumor mutation burden (TMB) were also calculated. Results: A total of 13 276 patients with CRC were enrolled, and 239 patients with sMPCC (mean [SD] age, 63.3 [12.2] years; 173 men [72.4%]) with available clinical data were evaluated. Seventy-eight patients with sMPCC and 94 with SPCRC also underwent next-generation sequencing (NGS)–based molecular testing. The deficient MMR (dMMR)/MSI-H frequencies in sMPCC were significantly higher than those in SPCRC, which was confirmed by both IHC (50 of 239 patients vs 872 of 13 037 patients) and NGS (17 of 78 patients vs 5 of 94 patients). According to the MMR/MSI status of different lesions in patients with sMPCC, they were further divided into 3 subgroups: all dMMR/MSI-H, dMMR/MSI-H and proficient MMR (pMMR)/microsatellite stability (MSS), and all pMMR/MSS. The EGFR and PIK3CA variants were more common, whereas TP53 variants were less prevalent in patients with sMPCC than in those with SPCRC. Moreover, higher tumor mutation burden was associated with higher MSI in patients with sMPCC rather than in those with SPCRC. Conclusions and Relevance: In this cohort study of sMPCC, the incidence of dMMR/MSI-H in patients with sMPCC was significantly higher than that in patients with SPCRC. These findings suggest that sMPCC can be classified into 3 subgroups according to the MMR/MSI status of each lesion, which might be applied to guide personalized therapies for better disease management.
- Subjects
SEROTYPING; GENETIC mutation; SEQUENCE analysis; CARCINOGENESIS; IMMUNOHISTOCHEMISTRY; ONCOGENES; COLORECTAL cancer; MOLECULAR biology; TUMOR classification; SYMPTOMS
- Publication
JAMA Network Open, 2022, Vol 5, Issue 11, pe2243457
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2022.43457