Nickan Research Institute Immunopathologia Persa 2423-8015 12 1 2026 01 01 Immunohistochemical biomarkers for predicting malignant transformation in oral leukoplakia and lichen planus: a systematic review study e43919 e43919 10.34172/ipp.2025.43919 EN Sarah AlFarabi Ali https://orcid.org/0000-0003-0117-6596 Ahoud Jazzar https://orcid.org/0000-0002-0226-3512 Yasmin Hisham Mair https://orcid.org/0009-0002-3365-2673 Sara Akeel https://orcid.org/0000-0001-8006-1185 Maha Talal Alsharif https://orcid.org/0000-0002-0997-7171 Hebah AlDehlawi https://orcid.org/0009-0007-8910-0348 Nada A. Alhindi https://orcid.org/0000-0002-2388-7586 Soulafa Adnan Almazrooa https://orcid.org/0000-0001-6350-3578 Journal Article 10.34172/ipp.2025.43919 2025 05 02 2025 08 18 Introduction: Oral leukoplakia (OLK) and oral lichen planus (OLP) are recognized as potentially malignant disorders with varying risks of progression to oral squamous cell carcinoma (OSCC). Immunohistochemical (IHC) biomarkers have been extensively studied to identify predictive markers for malignant transformation in these lesions. Objectives: This systematic review synthesizes current evidence on IHC biomarkers associated with malignant progression in OLK and OLP. Materials and Methods: In this systematic review study, a systematic literature search was conducted across databases, including PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar search engine up to April 2025. Studies included were those investigating IHC biomarkers in OLK and OLP with reported malignant transformation outcomes. Results: This systematic review included 10 studies with a total of 549 participants. The most frequently assessed IHC markers were B-cell lymphoma 2 (Bcl-2), p53, Ki-67, Bcl-2-associated X protein (Bax), survivin, mouse double minute 2 homolog (MDM2), and proliferating cell nuclear antigen (PCNA). Bcl-2 was the predominant marker, evaluated in 9 studies, followed by p53 was examined in 7, Ki-67 in 4, and Bax in 3 studies. Less commonly studied markers included survivin, MDM2, PCNA, and p21, each reported in a single study. Conclusion: Although Bcl-2 and p53 emerge as the most significant IHC markers for predicting malignant transformation in oral premalignant lesions due to their roles in apoptosis and tumor suppression, the Ki-67 and Bax biomarkers contribute important information on cell proliferation and apoptotic balance, while markers like survivin, MDM2, PCNA, and p21 are less commonly studied but may have specialized roles. Overall, a panel of these biomarkers, especially Bcl-2 and p53, shows strong potential for improving risk assessment and guiding clinical management of OLK and OLP. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO (International Prospective Register of Systematic Reviews) (ID: CRD420251063588) and Research Registry (UIN: reviewregistry2021) websites.