Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Oncology. 2024;102(2):157-167. doi: 10.1159/000533406. Epub 2023 Sep 12.
Mismatch repair (MMR) deficiency represents a biomarker and therapeutic target in various neoplasms, but its role in biliary tract cancers (BTCs) remains misunderstood.
MMR status was retrospectively assessed using immunohistochemistry in 163-BTCs patients. We identified MMR proficiency (pMMR)/deficiency (dMMR) according to the loss of MMR proteins (MLH1, PMS2, MSH2, MSH6). The primary objective of the study was to assess the incidence of dMMR in BTCs; the secondary purpose was to explore its association with prognosis and clinical features.
dMMR was recorded in 9 patients, and it was strongly associated with mucinous histology (p < 0.01). Regarding the prognostic effect, in 122-radically resected patients, disease-free survival (DFS) resulted significantly shorter in dMMR patients compared to pMMR patients (10.7 vs. 31.3 months, p = 0.025) and so did nodal status (48.2 vs. 15.3 months in N0 vs. N+) (p < 0.01). Moreover, dMMR confirmed its prognostic role in terms of DFS at multivariate analysis (p = 0.03), together with nodal status (p = 0.01), and resection margin (p = 0.03). In 103 M+ patients (encompassing 41 metastatic de novo and 62 recurred after surgery patients) there were not differences between dMMR and pMMR regarding survival analyses.
dMMR status is strongly correlated with mucinous histology and represents an independent prognostic factor in terms of disease relapse in patients with resected BTC.
MMR may play an independent role in promoting an aggressive behaviour in patients with radically resected BTC. These results could be useful in improving the selection of patients after resection and, above all, should justify the evaluation of MMR status as a therapeutic target in BTC, especially in patients with atypical histology.
错配修复（MMR）缺陷是多种肿瘤的生物标志物和治疗靶点，但在胆道肿瘤（BTC）中的作用仍未被充分理解。
对 163 名 BTC 患者的组织标本进行回顾性免疫组化评估 MMR 状态。我们根据 MMR 蛋白（MLH1、PMS2、MSH2、MSH6）缺失来确定 MMR 功能正常（pMMR）/缺陷（dMMR）。本研究的主要目的是评估 BTC 中 dMMR 的发生率；次要目的是探讨其与预后和临床特征的关系。
在 9 名患者中记录到 dMMR，且其与黏液性组织学显著相关（p < 0.01）。在 122 名接受根治性切除的患者中，与 pMMR 患者相比，dMMR 患者的无病生存期（DFS）显著缩短（10.7 与 31.3 个月，p = 0.025），且淋巴结状态（N0 与 N+）也显著缩短（48.2 与 15.3 个月，p < 0.01）。此外，dMMR 在多变量分析中证实了其在 DFS 方面的预后作用（p = 0.03），同时与淋巴结状态（p = 0.01）和切缘状态（p = 0.03）相关。在 103 名 M+患者（包括 41 名初诊转移性患者和 62 名手术后复发患者）中，dMMR 和 pMMR 之间的生存分析无差异。
dMMR 状态与黏液性组织学密切相关，是切除后 BTC 患者疾病复发的独立预后因素。这些结果可能有助于改善手术后患者的选择，尤其是在组织学不典型的患者中，应该证明评估 MMR 状态作为 BTC 的治疗靶点是合理的。
MMR 可能在促进根治性切除的 BTC 患者的侵袭性行为方面发挥独立作用。
