Supplementary Material for: Clinicopathological Features Associated with Microsatellite Instability/Mismatch Repair Deficiency in Uterine Carcinosarcoma: A Quantitative Systematic Review

<b><i>Introduction:</i></b> Recent studies suggested that microsatellite instability/mismatch repair deficiency (MSI/MMR-d) might define a clinicopathologically distinct subset of uterine carcinosarcomas (UCSs). <b><i>Objective:</i></b> The aim of this study was to compare clinicopathological features between MSI/MMR-d and microsatellite-stable/mismatch repair-proficient (MSS/MMR-p) UCSs. <b><i>Methods:</i></b> A quantitative systematic review was performed by searching electronic databases from January 2000 to January 2021. All studies assessing MSI/MMR status in UCS were included. Odds ratio (OR) with a significant two-tailed <i>p</i> value &lt;0.05 was used to assess the association of MSI/MMR-d with clinicopathological features. <b><i>Results:</i></b> Eleven studies with 783 patients were included. MSI/MMR-d was directly associated with endometrioid (pure: <i>p</i> &lt; 0.001; pure + mixed: <i>p</i> &lt; 0.001), undifferentiated/dedifferentiated (<i>p</i> &lt; 0.001), and clear cell carcinoma component (<i>p</i> = 0.046), and inversely associated with age &gt;60 (<i>p</i> = 0.034), serous carcinoma component (pure: <i>p</i> &lt; 0.001; pure + mixed: <i>p</i> &lt; 0.001), heterologous sarcoma component (<i>p</i> = 0.027), <i>TP53</i>-mutation/p53-abnormal expression (<i>p</i> &lt; 0.001), and recurrence (<i>p</i> &lt; 0.001). MSI/MMR-d showed no significant association with advanced FIGO stage (OR = 1.259; <i>p</i> = 0.517), low-grade carcinoma component (pure: <i>p</i> = 0.596; pure + mixed: <i>p</i> = 0.307), mixed carcinoma component (<i>p</i> = 1), and proportion of patients “dead of disease” (<i>p</i> = 0.352), “alive with disease” (<i>p</i> = 1) or with “no evidence of disease” (<i>p</i> = 0.458). <b><i>Conclusion:</i></b> MSI/MMR-d UCSs show younger age, more common endometrioid, undifferentiated or clear cell carcinoma component, and less common serous carcinoma component, heterologous sarcoma component, and <i>TP53</i> mutation than MSS/MMR-p UCSs. Given the discrepancy between recurrence rate and oncologic outcomes at the last follow-up, further studies are necessary to define whether MSI/MMR-d UCSs have better prognosis.

引言：近年研究显示，微卫星不稳定/错配修复缺陷（microsatellite instability/mismatch repair deficiency, MSI/MMR-d）可界定子宫癌肉瘤（uterine carcinosarcomas, UCS）的一类临床病理特征独特的亚型。
研究目的：本研究旨在对比MSI/MMR-d与微卫星稳定/错配修复完整（microsatellite-stable/mismatch repair-proficient, MSS/MMR-p）子宫癌肉瘤的临床病理特征。
研究方法：本研究通过检索2000年1月至2021年1月的电子数据库，开展定量系统综述。纳入所有评估子宫癌肉瘤MSI/MMR状态的相关研究。采用双侧检验p值<0.05的比值比（odds ratio, OR），分析MSI/MMR-d与临床病理特征的相关性。
研究结果：最终纳入11项研究，共计783例患者。MSI/MMR-d与子宫内膜样（单纯型：p<0.001；单纯型+混合型：p<0.001）、未分化/去分化（p<0.001）及透明细胞癌成分呈正相关，与年龄>60岁（p=0.034）、浆液性癌成分（单纯型：p<0.001；单纯型+混合型：p<0.001）、异源性肉瘤成分（p=0.027）、TP53突变/p53异常表达（p<0.001）及复发（p<0.001）呈负相关。MSI/MMR-d与国际妇产科联盟（International Federation of Gynecology and Obstetrics, FIGO）晚期分期（OR=1.259；p=0.517）、低级别癌成分（单纯型：p=0.596；单纯型+混合型：p=0.307）、混合型癌成分（p=1），以及“死于疾病”（p=0.352）、“带瘤生存”（p=1）或“无病生存”（p=0.458）的患者比例均无显著相关性。
研究结论：相较于MSS/MMR-p子宫癌肉瘤，MSI/MMR-d阳性子宫癌肉瘤患者发病年龄更轻，更常伴子宫内膜样、未分化或透明细胞癌成分，而浆液性癌成分、异源性肉瘤成分及TP53突变的发生率更低。鉴于复发率与末次随访的肿瘤学结局存在差异，尚需开展进一步研究以明确MSI/MMR-d阳性子宫癌肉瘤是否具有更优的预后。