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

Abstract

<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 &#x3c;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> &#x3c; 0.001; pure + mixed: <i>p</i> &#x3c; 0.001), undifferentiated/dedifferentiated (<i>p</i> &#x3c; 0.001), and clear cell carcinoma component (<i>p</i> = 0.046), and inversely associated with age &#x3e;60 (<i>p</i> = 0.034), serous carcinoma component (pure: <i>p</i> &#x3c; 0.001; pure + mixed: <i>p</i> &#x3c; 0.001), heterologous sarcoma component (<i>p</i> = 0.027), <i>TP53</i>-mutation/p53-abnormal expression (<i>p</i> &#x3c; 0.001), and recurrence (<i>p</i> &#x3c; 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.