Supplementary Material for: Mismatch repair deficiency in biliary tract cancer: prognostic implications and correlation with histology.

Introduction: Mismatch repair (MMR) deficiency represents a biomarker and therapeutic target in various neoplasms, but its role in biliary tract cancers (BTCs) remains misunderstood.
Methods: 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 (MLH-1, PMS-2, MSH-2, MSH-6). 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.
Results: 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 weren’t differences between dMMR and pMMR regarding survival analyses.
Discussion/Conclusions: dMMR status is strongly correlated with mucinous histology and represents an independent prognostic factor in terms of disease-relapse in patients with resected BTC.

引言：错配修复（Mismatch repair, MMR）缺陷是多种恶性肿瘤的生物标志物与治疗靶点，但其在胆道系统肿瘤（biliary tract cancers, BTCs）中的作用仍未被充分阐明。
方法：本研究采用免疫组化法，对163例BTC患者的MMR状态进行回顾性评估。根据MLH-1、PMS-2、MSH-2、MSH-6这4种MMR蛋白的缺失情况，将患者划分为MMR功能正常（pMMR）组与MMR功能缺陷（dMMR）组。本研究的主要研究目标为评估BTC患者中dMMR的发生率；次要研究目标为探讨dMMR与患者预后及临床特征的相关性。
结果：本研究共检出9例dMMR患者，其与黏液样组织学类型显著相关（p<0.01）。在122例接受根治性切除的患者中，dMMR组患者的无病生存期（disease-free-survival, DFS）显著短于pMMR组（10.7个月 vs 31.3个月，p=0.025）；淋巴结状态同样对DFS存在显著影响：N0期患者的DFS为48.2个月，N+期患者为15.3个月（p<0.01）。多因素分析显示，dMMR、淋巴结状态（p=0.01）及手术切缘状态（p=0.03）均为影响DFS的独立预后因素（dMMR：p=0.03）。在103例M+患者（包含41例初发转移性患者与62例术后复发患者）中，dMMR组与pMMR组的生存分析未发现显著差异。
讨论与结论：dMMR状态与黏液样组织学类型显著相关，且可作为接受根治性切除的BTC患者术后复发的独立预后因素。