MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL ANALYSIS OF LATS, YAP, AND TEAD IN PROLIFERATIVE VERRUCOUS LEUKOPLAKIA
Keywords:
Oral Leukoplakia; Hippo Signaling Pathway; YAP Signaling Proteins; TEA Domain Transcription Factors.
Proliferative verrucous leukoplakia (PVL) exhibits a variable clinical course, histopathological heterogeneity, high recurrence and malignant transformation rates, as well as therapeutic resistance, making its diagnosis and management particularly challenging. In this context, the identification of biomarkers capable of aiding in the prediction of disease progression and risk stratification becomes essential. The Hippo signaling pathway (HP) has been associated with tumor progression, potentially contributing to carcinogenesis by promoting cell proliferation and evasion of apoptosis, thus emerging as a promising target for investigation in PVL. This study evaluated the immunoexpression of LATS, YAP, and TEAD proteins—key components of the HP—in PVL cases, aiming to correlate their expression with the different morphological patterns observed in these lesions. The sample consisted of 111 biopsies obtained from the lesions of 15 patients diagnosed with PVL. For morphological assessment, the grading systems based on the WHO (2022) classification and the criteria proposed by Thompson et al. (2021) were applied. Immunohistochemical analysis of LATS and YAP was performed using scores ranging from 0 to 3, while TEAD expression was assessed using scores from 0 to 2, based on intracellular localization (cytoplasmic and/or nuclear) and distribution throughout the epithelium. To analyze associations between the evaluated parameters, Fisher’s Exact Test was applied. Non-parametric tests were conducted to assess differences and correlations between the markers and clinicopathological parameters, adopting a significance level of 5%. According to WHO (2022) criteria, most lesions were classified as mild (45.9%) or moderate (38.7%) epithelial dysplasia, and as pattern I (64.9%) according to Thompson et al. (2021), with a statistically significant negative concordance between the two systems (k = –0.057; p = 0.042). YAP expression showed a statistically significant variation among the groups (p = 0.009), with pattern II of Thompson et al. (2021) presenting a higher median compared to pattern I (p = 0.005). LATS showed a similar trend, although without statistical significance, suggesting a possible association of HP activation with the increased epithelial proliferation observed in this pattern. Cases with nuclear expression of YAP exhibited higher TEAD scores (p = 0.030), indicating a possible functional activity of YAP as a transcriptional cofactor, activating the TEAD transcription factor. Additionally, a statistically significant positive correlation was observed among all combinations of the proteins evaluated. Taken together, these findings suggest a role for the Hippo pathway in PVL.