MMR markers correlate with clinical outcome in patients with esophageal squamous cell carcinoma.

IF 2.3 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY International Journal of Biological Markers Pub Date : 2023-06-01 DOI:10.1177/03936155231165068
Takuro Yamauchi, Fumiyoshi Fujishima, Junichi Tsunokake, Atsushi Kunimitsu, Ryujiro Akaishi, Yohei Ozawa, Toshiaki Fukutomi, Hiroshi Okamoto, Chiaki Sato, Yusuke Taniyama, Takashi Kamei, Ryo Ichinohasama, Hironobu Sasano
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Abstract

Background: The DNA mismatch repair system is one of the defense mechanisms in the body, and the inactivation of mismatch repair plays a pivotal role in secondary carcinogenesis and progression. However, the significance of mismatch repair in esophageal squamous cell carcinoma (ESCC) has not been established. In this study, we explored the diagnostic and prognostic significance of mismatch repair markers, mutL homologue 1 (MLH1), post-meiotic segregation increased 2 (PMS2), mutS homologue 2 (MSH2), and mutS homologue 6 (MSH6), in patients with ESCC.

Methods: We used a notation based on the proportion of immunoreactivity/expression for immunohistochemistry (PRIME notation), which allows the comparison of mismatch repair expression by assigning a score to PRIME notation. MLH1, PMS2, MSH2, and MSH6 were examined immunohistochemically in 189 surgically resected ESCC specimens.

Results: A total of 100/189 patients with ESCC (53%) received preoperative chemotherapy. The rates of ESCC cases with decreased mismatch repair status were 13.2%, 15.3%, 24.8%, and 12.6% for MLH1, PMS2, MSH2, and MSH6, respectively. The decreased status of individual mismatch repair markers was significantly correlated with worse prognosis in patients with ESCC. Additionally, MSH2, MSH6, and PMS2 were significantly associated with response to preoperative chemotherapy. Multivariate analysis revealed that MLH1, PMS2, and MSH2 are independent prognostic factors.

Conclusion: Our results suggest that mismatch repair is a prognostic biomarker for ESCC and could contribute to the selection of appropriate adjuvant therapy for patients with ESCC.

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MMR标志物与食管鳞状细胞癌患者的临床预后相关。
背景:DNA错配修复系统是机体的防御机制之一,错配修复失活在继发性癌的发生和发展中起着关键作用。然而,错配修复在食管鳞状细胞癌(ESCC)中的意义尚未确定。在这项研究中,我们探讨了错配修复标记,mutL同源物1 (MLH1),减数分裂后分离增加2 (PMS2), mutS同源物2 (MSH2)和mutS同源物6 (MSH6)在ESCC患者中的诊断和预后意义。方法:我们使用基于免疫组织化学免疫反应性/表达比例的记谱法(PRIME记谱法),通过对PRIME记谱法评分,可以比较错配修复表达。对189例手术切除的ESCC标本进行了MLH1、PMS2、MSH2和MSH6免疫组化检测。结果:共有100/189例ESCC患者(53%)接受了术前化疗。MLH1、PMS2、MSH2和MSH6错配修复状态降低的ESCC病例比例分别为13.2%、15.3%、24.8%和12.6%。个体错配修复标记的降低与ESCC患者的预后不良显著相关。此外,MSH2、MSH6和PMS2与术前化疗反应显著相关。多因素分析显示,MLH1、PMS2和MSH2是独立的预后因素。结论:我们的研究结果表明,错配修复是ESCC的预后生物标志物,可以帮助ESCC患者选择合适的辅助治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International Journal of Biological Markers
International Journal of Biological Markers 医学-生物工程与应用微生物
CiteScore
4.10
自引率
0.00%
发文量
43
期刊介绍: IJBM is an international, online only, peer-reviewed Journal, which publishes original research and critical reviews primarily focused on cancer biomarkers. IJBM targets advanced topics regarding the application of biomarkers in oncology and is dedicated to solid tumors in adult subjects. The clinical scenarios of interests are screening and early diagnosis of cancer, prognostic assessment, prediction of the response to and monitoring of treatment.
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