Microsatellite instability as a marker of prognosis: a systematic review and meta-analysis of endometrioid endometrial cancer survival data

Abstract

Introduction: To investigate whether microsatellite instability (MSI) is an important prognostic biomarker for endometrioid endometrial cancer (EEC).

Methods: The PubMed, EMBASE, and the Cochrane Cooperative Library databases were searched from inception to July 2021. Overall survival, disease-free survival, progression-free survival, EEC-specific survival, recurrence-free survival, and the recurrence rate were pooled to analyze the correlation between MSI and EEC. In addition, Egger's regression analysis and Begg's test were used to detect publication bias.

Results: 17 studies met the inclusion criteria and were included in our meta-analysis with a sample size of 4723, and the included patients with endometrioid cancer (EC) all were EEC. The pooled hazard ratios (HR) in patients with EEC showed that MSI was significantly associated with shorter overall survival [HR = 1.37, 95% confidence interval (CI) (1.00-1.86), p = 0.048, I² = 60.6%], shorter disease-free survival [HR = 1.99, 95% CI (1.31-3.01), p = 0.000, I² = 67.2%], shorter EEC-specific survival [HR = 2.07, 95% CI (1.35-3.18), p = 0.001, I² = 31.6%] and a higher recurrence rate [Odds ratios (OR) = 2.72, 95% CI (1.56-4.76), p = 0.000, I² = 0.0%]. In the early-stage EEC subgroup, MSI was significantly associated with shorter overall survival [HR = 1.47, 95% CI (1.11-1.95), p = 0.07], shorter disease-free survival [HR = 4.17, 95% CI (2.37-7.41), p = 0.000], and shorter progression-free survival [HR = 2.41, 95% CI (1.05-5.54), p = 0.039]. No significant heterogeneity was observed in overall survival (I² = 20.9%), disease-free survival (I² = 0.0%), or progression-free survival (I² = 0.0%) in patients with early-stage EEC. Meanwhile, publication bias was not observed, and the p-value for Egger's test of overall survival, disease-free survival, and EEC-specific survival were p = 0.131, p = 0.068, and p = 0.987, respectively.

Conclusion: MSI is likely an important biomarker for poor prognosis in patients with EEC, and this correlation is even more certain in patients with early-stage EEC.

Keywords: Early-stage endometrioid endometrial cancer; Endometrioid endometrial cancer; Meta-analysis; Microsatellite instability; Prognosis.