# Ovo-Like Transcriptional Repressor 1 (OVOL1) Expression in Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma: Diagnostic and Prognostic Insights

## TL;DR

This study explores the role of OVOL1 in benign and malignant salivary gland tumors, finding that lower OVOL1 levels are linked to more aggressive cancer behavior.

## Contribution

The study is the first to investigate OVOL1 expression in pleomorphic adenoma and carcinoma ex pleomorphic adenoma for diagnostic and prognostic purposes.

## Key findings

- OVOL1 expression was significantly higher in benign pleomorphic adenoma than in malignant carcinoma ex pleomorphic adenoma.
- Low OVOL1 levels were associated with high-grade and recurrent carcinoma ex pleomorphic adenoma, indicating more aggressive tumor behavior.
- OVOL1 shows potential as a biomarker to distinguish between benign and malignant salivary gland tumors.

## Abstract

Introduction

Pleomorphic adenoma (PA) is the most common benign tumor of the salivary glands and has the potential for malignant transformation into carcinoma ex pleomorphic adenoma (CXPA). Ovo-like transcriptional repressor 1 (OVOL1) is a transcription factor that regulates epithelial differentiation by suppressing epithelial-mesenchymal transition (EMT) and promoting mesenchymal-epithelial transition (MET). OVOL1 expression is regulated by the Wnt signaling pathway, a central regulator of epithelial stem cell development, maintenance, and differentiation. While several transcription factors are implicated in EMT/MET, OVOL1 is of particular interest because of its potential dual role in maintaining epithelial identity and modulating tumor behavior. Its dysregulation has been associated with adverse prognosis in several cancers. Therefore, this study aims to investigate OVOL1 expression in PA and CXPA to clarify its potential role in the transition from benign to malignant lesions and to improve the assessment of tumor biological behavior.

Materials and methods

This retrospective comparative cohort study included 40 cases, 20 cases of PA and 20 cases of CXPA, diagnosed between 2017 and 2024, retrieved from the archive of the Pathology Laboratory at Mansoura University’s Oncology Center. Owing to the rarity of CXPA, all eligible cases during the study period were included. To provide a balanced comparator group and minimize selection bias, an equal number of PA cases were consecutively selected from the same archive and timeframe. Clinical data were obtained from electronic medical records. Hematoxylin and eosin-stained slides were reviewed by expert pathologists to confirm the diagnosis. Morphological subtyping of CXPA was performed according to the most recent WHO Classification of head and neck tumors. OVOL1 immunohistochemical expression was evaluated in both PA and CXPA using a combined semi-quantitative immunoreactive score (IRS) and quantitative digital image analysis (ImageJ software), ensuring greater objectivity and reproducibility. Correlations with clinicopathological features were examined using appropriate statistical tests.

Results

All studied PA and CXPA cases were OVOL1-positive with different levels of expression. PA cases predominantly showed high expression, while most CXPA demonstrated low levels, with a significant difference between the two groups. Low OVOL1 expression was more frequent in high-grade and recurrent CXPA, suggesting a link with tumor aggressiveness.

Conclusion

Our results suggest the potential of OVOL1 as a diagnostic and prognostic biomarker, particularly in distinguishing PA from CXPA, and as a promising indicator of tumor aggressiveness and malignant transformation. While these findings are limited by the small cohort size, they provide preliminary evidence that warrants validation in larger, multi-institutional studies exploring their clinical significance and underlying molecular mechanisms.