Atlas of Tumor and Tumor Microenvironment Cells of Lymphovascular Space Invasion (LVSI) in High-Grade Serous Endometrial Adenocarcinoma: A Case Study

Abstract

Lymphovascular invasion (LVSI) is defined as the presence of tumor cells within a definite endothelial-lined space (lymphatics or blood vessels) in the organ surrounding invasive carcinoma. The presence of LVI is associated with an increased risk of lymph nodes and distant metastases. Lymphovascular invasion is described as cancer within blood or lymph vessels and is an independent risk factor for metastasis, recurrence, and mortality. This study aims to present the marker-based immunohistological characterization of cells around LVSI in a high-grade adenocarcinoma of the endometrium to build a cellular atlas of cells of LVSI. A cellular characterization of the cells around lymphovascular space invasion in a 67-year-old female patient with invasive high-grade serous endometrial adenocarcinomas is presented. Resected tumor tissue from a consented patient with invasive high-grade serous endometrial adenocarcinoma was obtained within an hour of surgery. The expressions of the epithelial markers (CK8, 18, and EpCAM), LCA (leukocyte common antigen) marker (CD45), proliferation marker (Ki67), apoptosis markers (cleaved PARP and cleaved caspase3), immune cell markers (CD3, CD4, CD8, CD56, CD68, CD163, FoxP3, PD-1, PD-L1), pro-inflammatory marker (IL-12-RB2), and fibroblast/mesenchyme markers (S100A7, SMA, and TE-7) of the resected tissue on the IHC stains were evaluated and scored by a pathologist. Acknowledging the deterministic role of LVSI in a high-grade adenocarcinoma of the endometrium, our study presents the first marker-based immunohistological atlas of the tumor and TME compartments in the context of epithelial cell markers, proliferation markers, apoptosis markers, macrophage markers, and fibroblast markers. Our study demonstrates that an aggressive disease like a high-grade adenocarcinoma of the endometrium inflicts the pro-metastatic event of LVSI by involving the immune landscape of both tumor and TME. This study demonstrates, for the first time, that the tumor cells within LVSI are positive for IL-12R-B2 and S100A4.