MMR 标志物与食管鳞癌患者的临床结局相关。

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

机构信息

Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.

Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.

出版信息

Int J Biol Markers. 2023 Jun;38(2):105-113. doi: 10.1177/03936155231165068. Epub 2023 Apr 3.

DOI:10.1177/03936155231165068

PMID:37009661

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.

摘要

背景

DNA 错配修复系统是机体的防御机制之一，错配修复失活在次级致癌作用和进展中起着关键作用。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志物 MLH1、post-meiotic segregation increased 2（PMS2）、mutS homologue 2（MSH2）和 mutS homologue 6（MSH6）在 ESCC 患者中的诊断和预后意义。

方法

我们使用了基于免疫组化（IHC）反应性/表达比例的符号（PRIME 符号），通过为 PRIME 符号分配分数来比较错配修复表达，从而允许比较错配修复表达。在 189 例手术切除的 ESCC 标本中进行了 MLH1、PMS2、MSH2 和 MSH6 的免疫组化检查。

结果

共有 100/189 例 ESCC 患者（53%）接受了术前化疗。MLH1、PMS2、MSH2 和 MSH6 缺失错配修复状态的 ESCC 病例分别为 13.2%、15.3%、24.8%和 12.6%。个别错配修复标志物的缺失状态与 ESCC 患者的预后显著相关。此外，MSH2、MSH6 和 PMS2 与术前化疗的反应显著相关。多变量分析显示 MLH1、PMS2 和 MSH2 是独立的预后因素。