Clinicopathological significance and prognostic value of intratumoral and peritumoral lymphocytes in endometrial cancer patients.

Abstract

e17116 Background: The characterization and prognostic relevance of immune cells in the tumor microenvironment of endometrial cancer (EC) remain unknown. Our aims are to analyze the presence of tumor infiltrating lymphocytes (TIL) and peritumoral lymphocytes (PTL) in tumoral tissue of patients with EC, and to identify the correlation between TILs and PTLs subsets with clinicopathologic features and its prognostic value Methods: CD3, CD4, CD8, CD20, and FOXP-3 was determined by immunohistochemestry (IHQ). A 4-point score was defined based on TIL counts per highpowered field: (negative, low, moderate, and high). We used 10% positive peritumoral lymphocytes as a low-high cutoff value. POLE mutation was identified by Sanger sequencing of the exonuclease domain (exons 9-14). Analysis of mismatch repair expression and TP53 gene mutation status were assessed. Results from IHQ and analysis mutation were correlated with clinicopathological parameters and survival. Results: We recovered tumor samples from 68 FIGO stage I–IV EC patients. POLE mutations were identified in 5 of 44 (11.4%) EC analyzed. Microsatellite instability (MSI) and TP53 mutation were found in 45% and 25 % of cases respectively. According PTL, MSI tumors were significantly associated with low CD4+ (p = 0.01). High CD8+ was significantly associated with endometrioid grade 1-2 tumors (p = 0.04). Low FOXP3+ was significantly associated with endometrioid grade 1-2 (p = 0.02), MSS tumors (p < 0.01), FIGO stage I-II (p < 0.01), POLE WT (p < 0.01), TP53 WT (p < 0.01), and negative lymphovascular space invasion (p < 0.01). Negative CD20+ TIL was associated with endometrioid grade 1-2 tumors (p < 0.01) and ≥50% myometrial invasion (p = 0.03). Moderate CD8+ TIL was associated with lower tumor stage (p = 0.01). High CD8+ TIL was associated with better 5-year overall survival (OS) rate (high: 100 % vs. low: 53%; p = 0.003). No significant association was observed between POLE status, TP53 status, MMR expression and survival. Conclusions: Regulatory and cytotoxic T cells subsets differs in EC patients. High CD8+ TILs was significantly associated with better 5-year OS.

Tumour microenvironment and PD-L1 expression in endometrial carcinoma

“…CD8+ stromal and tumour cells were found most frequently in the High-Risk Intermediate Group, according to ESMO stratification criteria. This finding partly coincides with other studies regarding FIGO grade or myometrium invasion 13 . Furthermore, recent research revealed that tumour stage, FIGO grade, and high densities of tumour CD8+ cells are independent predictors of overall survival 14 .…”

The prevalence and prognostic impact of tumor-infiltrating lymphocytes in uterine carcinosarcoma

“…FOXP3 is the most specific marker for Treg cells and, often associated with a negative impact on survival in several types of cancer, is likely to have an important role in suppressing anti-tumor immunity [ 30 , 31 ]. Ore-Arce et al [ 32 ] also reported that high CD8+ TILs was significantly associated with better 5-year OS in 68 women with FIGO stage I–IV endometrial cancer. Conversely, our current results suggested that high CD8/FOXP3_S and CD4/FOXP3_S ratios significantly yielded poorer survival outcomes.…”