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

**Authors:** Raed Sulaiman, Adam Dale, Xiaoqian Lin, Jennifer C. Aske, Kris Gaster, David Starks, Luis Rojas Espaillat, Pradip De, Nandini Dey

PMC · DOI: 10.3390/ijms25063441 · International Journal of Molecular Sciences · 2024-03-19

## TL;DR

This study creates a detailed map of tumor and surrounding cells involved in lymphovascular invasion in a high-grade endometrial cancer case.

## Contribution

The first marker-based immunohistological atlas of tumor and TME cells in LVSI of high-grade endometrial adenocarcinoma.

## Key findings

- Tumor cells within LVSI are positive for IL-12R-B2 and S100A4.
- LVSI involves changes in the immune landscape of both tumor and tumor microenvironment.
- Expressions of epithelial, proliferation, apoptosis, and immune markers were characterized in LVSI.

## 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.

## Linked entities

- **Genes:** KRT8 (keratin 8) [NCBI Gene 3856], KRT18 (keratin 18) [NCBI Gene 3875], EPCAM (epithelial cell adhesion molecule) [NCBI Gene 4072], PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788], Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345], cd.3 (Cd.3 conserved hypothetical protein) [NCBI Gene 1258599], CD4 (CD4 molecule) [NCBI Gene 920], CD8A (CD8 subunit alpha) [NCBI Gene 925], NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684], CD68 (CD68 molecule) [NCBI Gene 968], CD163 (CD163 molecule) [NCBI Gene 9332], FOXP3 (forkhead box P3) [NCBI Gene 50943], PDCD1 (programmed cell death 1) [NCBI Gene 5133], CD274 (CD274 molecule) [NCBI Gene 29126], IL12RB2 (interleukin 12 receptor subunit beta 2) [NCBI Gene 3595], S100A7 (S100 calcium binding protein A7) [NCBI Gene 6278], SMN1 (survival of motor neuron 1, telomeric) [NCBI Gene 6606], TE7 (membrane protein TE7) [NCBI Gene 26122581], S100A4 (S100 calcium binding protein A4) [NCBI Gene 6275]

## Full-text entities

- **Genes:** CD68 (CD68 molecule) [NCBI Gene 968] {aka GP110, LAMP4, SCARD1}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, IL12RB2 (interleukin 12 receptor subunit beta 2) [NCBI Gene 3595], FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, S100A4 (S100 calcium binding protein A4) [NCBI Gene 6275] {aka 18A2, 42A, CAPL, FSP1, MTS1, P9KA}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, COL11A2 (collagen type XI alpha 2 chain) [NCBI Gene 1302] {aka DFNA13, DFNB53, FBCG2, HKE5, OSMEDA, OSMEDB}, CD163 (CD163 molecule) [NCBI Gene 9332] {aka M130, MM130, SCARI1}, EPCAM (epithelial cell adhesion molecule) [NCBI Gene 4072] {aka Ber-Ep4, BerEp4, DIAR5, EGP-2, EGP314, EGP40}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, SMN1 (survival of motor neuron 1, telomeric) [NCBI Gene 6606] {aka BCD541, GEMIN1, SMA, SMA1, SMA2, SMA3}, S100A7 (S100 calcium binding protein A7) [NCBI Gene 6278] {aka PSOR1, S100A7c}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, RBL2 (RB transcriptional corepressor like 2) [NCBI Gene 5934] {aka BRUWAG, P130, Rb2}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}
- **Diseases:** lymph nodes and distant metastases (MESH:D008207), Tumor (MESH:D009369), metastasis (MESH:D009362), inflammatory (MESH:D007249), LVSI (MESH:D009361), Endometrial Adenocarcinoma (MESH:D016889)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

20 figures with captions in the complete paper: https://tomesphere.com/paper/PMC10970754/full.md

## References

25 references — full list in the complete paper: https://tomesphere.com/paper/PMC10970754/full.md

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Source: https://tomesphere.com/paper/PMC10970754