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

Introduction: Recent studies suggested that microsatellite instability/mismatch repair deficiency (MSI/MMR-d) might define a clinicopathologically distinct subset of uterine carcinosarcomas (UCSs).

Objective: The aim of this study was to compare clinicopathological features between MSI/MMR-d and microsatellite-stable/mismatch repair-proficient (MSS/MMR-p) UCSs.

Methods: 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 p value <0.05 was used to assess the association of MSI/MMR-d with clinicopathological features.

Results: Eleven studies with 783 patients were included. MSI/MMR-d was directly associated with endometrioid (pure: p < 0.001; pure + mixed: p < 0.001), undifferentiated/dedifferentiated (p < 0.001), and clear cell carcinoma component (p = 0.046), and inversely associated with age >60 (p = 0.034), serous carcinoma component (pure: p < 0.001; pure + mixed: p < 0.001), heterologous sarcoma component (p = 0.027), TP53-mutation/p53-abnormal expression (p < 0.001), and recurrence (p < 0.001). MSI/MMR-d showed no significant association with advanced FIGO stage (OR = 1.259; p = 0.517), low-grade carcinoma component (pure: p = 0.596; pure + mixed: p = 0.307), mixed carcinoma component (p = 1), and proportion of patients "dead of disease" (p = 0.352), "alive with disease" (p = 1) or with "no evidence of disease" (p = 0.458).

Conclusion: 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 TP53 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.