Substantial lymph-vascular space invasion (LVSI) as predictor of distant relapse and poor prognosis in low-risk early-stage endometrial cancer

e16551 Background: The proportion of patients receiving chemotherapy for endometrial cancer is increasing both in the adjuvant and advanced setting. The literature describes many prognostic immunohistochemical factors in early stage endometrial cancer, the majority of whom will not receive chemotherapy. The aim of this study was to describe the biomarker expression for endometrial tumours treated with chemotherapy and to assess what constitutes a favourable and unfavourable profile for this patient group. Methods: For a subset of patients with either endometrioid, serous or a mixed mullerian morphology treated with chemotherapy at our centre between 1996 and 2008 an immunohistochemical profile of 14 biomarkers was studied (ERα, Erβ1, Erβ2, PR, PRB, P53, Rb, E-cad, MDM2, MIB-1, E2F1, p16, p13, and p21). A univariate analysis using cox regression of potential prognostic factors was then carried out. Results: In total 199 patients received chemotherapy for endometrial cancer over the 12 year period studied. Two year survival from commencement of chemotherapy for patients receiving adjuvant treatment was 45.2% and palliative treatment 28.1%. The commonest histological subtypes were endometrioid adenocarcinoma (40%), serous carcinoma (24.1%) and mixed mullerian tumours (14.6%). For the subset of 35 patients 38.2% of patients had positive immunohistochemical staining for ERα, 53% for PR, 73.5% for p16, and 94% for E2F1. Good prognosis was predicted by the strength of staining for E2F1 (HR 0.757, CI 0.216/0.902, p = 0.025) and poor prognosis by p16 (HR 1.470, CI 1.040/2.077, p = 0.029). Conclusions: Positive staining for ERα and PR was of similar frequency to previous studies of early stage endometrial cancer and did not significantly influence prognosis. Good prognosis correlated with E2F1 expression and poor prognosis with p16. A greater proportion of patients had serous morphology compared to published series of early stage endometrial cancer. Further study of prognostic factors in larger numbers of patients and built into prospective randomised trials may allow the creation of a prognostic model and guide the development of future clinical trials of targeted therapy. No significant financial relationships to disclose.

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Microsatellite instability leads to poor prognosis in patients with early-stage endometrial cancer? a meta-analysis

10.21203/rs.3.rs-132471/v1 ◽

2020 ◽

Author(s):

Jingping Xiao ◽

Jisheng Wang ◽

Yuanyu Zhao ◽

Miaoquan He ◽

Jiang Du ◽

...

Keyword(s):

Endometrial Cancer ◽

Microsatellite Instability ◽

Publication Bias ◽

Poor Prognosis ◽

Early Stage ◽

Meta Analysis ◽

Significant Heterogeneity ◽

Free Survival ◽

Independent Marker ◽

Early Stage Endometrial Cancer

Abstract Background Poor prognosis of early-stage endometrial cancer (EC) is often accompanied by microsatellite instability (MSI). We hypothesized that MSI is an independent marker for poor prognosis of early-stage EC. To demonstrate this hypothesis, we evaluated the correlation between MSI and early-stage EC prognosis by meta-analysis. Methods Databases such as PubMed, EMBASE and the Cochrane Cooperative Library were searched from inception to October 2020, respectively. The disease-free survival (DFS), the overall survival (OS), and the progression-free survival (PFS) were pooled to analyze the correlation between MSI and prognosis in patients with early-stage EC. Besides, Egger's regression and Begg's test were used to detect Publication bias. Results There were 7 studies met the inclusion criteria and were enrolled in our meta-analysis with a sample size of 1150, and the included patients with early-stage EC were all endometrioid endometrial cancer (EEC). The pooled hazard ratios (HRs) in early-stage EC shows that MSI is significantly associated with lower DFS [HR = 3.90, 95%CI (2.81–6.99), p = 0.000], OS [HR = 1.48, 95%CI (1.12–1.96), p = 0.006], and PFS [HR = 2.41, 95%CI (1.05–5.52), p = 0.038]. There was no significant heterogeneity in the studies pooled analysis of DFS, OS, and PFS. There was also no statistical publication bias, the P-value of Egger`s test of OS and DFS is p = 0.535 and p = 0.639 respectively. Conclusion MSI is most likely an independent marker of poor prognosis in early-stage EC, and this correlation is even more significant in patients with EEC.

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