EZH2 Expression Correlates With T-Cell Infiltration in Oral Leukoplakia and Predicts Cancer Transformation

Divya Ganesh; Amal Dafar; Julia Niklasson; Ingrid Sandberg; Paulo Braz-Silva; Dipak Sapkota; Jenny Öhman; Daniel Giglio; Bengt Hasséus

doi:10.21873/anticanres.16302

EZH2 Expression Correlates With T-Cell Infiltration in Oral Leukoplakia and Predicts Cancer Transformation

Anticancer Res. 2023 Apr;43(4):1533-1542. doi: 10.21873/anticanres.16302.

Authors

Divya Ganesh¹, Amal Dafar^{1

2}, Julia Niklasson¹, Ingrid Sandberg¹, Paulo Braz-Silva^{3

4}, Dipak Sapkota⁵, Jenny Öhman^{1

6}, Daniel Giglio⁷, Bengt Hasséus^{8

9}

Affiliations

¹ Department of Oral Medicine and Pathology, Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Department of Oral and Maxillofacial Surgery, King Fahad General Hospital, Jeddah, Kingdom of Saudi Arabia.
³ Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil.
⁴ Laboratory of Virology, Institute of Tropical Medicine of São Paulo School of Medicine, São Paulo, Brazil.
⁵ Department of Oral Biology, University of Oslo, Oslo, Norway.
⁶ Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁷ Department of Oncology, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁸ Department of Oral Medicine and Pathology, Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; bengt.hasseus@gu.se.
⁹ Clinic of Oral Medicine, Public Dental Service, Region Västra Götaland, Gothenburg, Sweden.

PMID: 36974822
DOI: 10.21873/anticanres.16302

Abstract

Background/aim: The EZH2 complex is involved in cellular proliferation and modulates the immune response in cancer. Less is known about the importance of EZH2 in precancerous lesions such as oral leukoplakia (OL). The aim of the study was to explore the association between EZH2 expression, immune activation, and cancer transformation in OL.

Patients and methods: Analyses were retrospectively performed on nine OL cases that had undergone transformation to oral squamous cell carcinoma (OSCC; OL-ca) and nine that had not undergone transformation (OL-non). EZH2-expressing cells, CD3+ and CD8+ T cells, and CD1a+ Langerhans cells were visualized with immunohistofluorescence and counted.

Results: A moderate positive correlation between CD3- and EZH2-expressing and CD8- and EZH2-expressing cells in the epithelium was found (r=0.57, p=0.01; r=0.59, p=0.01). The number of EZH2-expressing cells in the epithelium of OL-ca was significantly higher compared to OL-non (p=0.0002). Cancer-free survival rates differed significantly between patients with EZH2^high compared to EZH2^low expression (p=0.001). EZH2^high expression in OL epithelium was associated with a 13-fold higher risk for developing OSCC (HR=12.8).

Conclusion: EZH2 expression in oral epithelium predicts OSCC transformation of OL and correlates with the level of T-cell infiltration.

Keywords: Oral potentially malignant disorder; biomarker; immune cells; oral cancer; polycomb group proteins.

MeSH terms

Carcinoma, Squamous Cell* / pathology
Cell Transformation, Neoplastic / metabolism
Enhancer of Zeste Homolog 2 Protein
Humans
Leukoplakia, Oral
Mouth Neoplasms* / pathology
Retrospective Studies

Substances

EZH2 protein, human
Enhancer of Zeste Homolog 2 Protein