Immunoexpression profile of LATS2 and YAP1 and its clinicopathological relevance in oral tongue squamous cell carcinoma.

OBJECTIVE

The objective of this study was to investigate the immunohistochemical expression of the Hippo pathway proteins LATS2 and YAP1 in oral tongue squamous cell carcinomas (OTSCCs) and normal oral mucosa (NOM), as well as potential relationships between them and clinicopathological characteristics and survival outcomes. MATERIALS AND

METHODS

Twenty-six cases of OTSCC and 8 samples of NOM were analyzed. Clinical data were obtained from medical records. Morphological assessment was based on the WHO (2005) grading system and the combined score of tumor cell nests (B) and tumor invasion depth (D) (BD model). Immunoexpression of LATS2 and YAP1 was determined by immunohistochemistry.

RESULTS

In NOMs, LATS2 expression was observed across all epithelial layers, with nuclear predominance, whereas YAP1 was observed in the basal and parabasal layers. YAP1 expression was significantly higher in OTSCCs (p < 0.001) and was significantly associated with the high-risk BD model (p = 0.034). OTSCCs with reduced LATS2 immunoexpression (p = 0.042) had poorer disease-free survival (DFS), while well-differentiated cases according to WHO presented better DFS outcome (p = 0.022). Multivariate analysis identified low LATS2 expression (HR 0.19; 95% CI 0.05–0.75; p = 0.017) and tumor size (HR 3.93; 95% CI 1.02–15.06; p = 0.046) as independent prognostic factors for 5-year DFS in OTSCC.

CONCLUSION

The functional alterations of LATS2 and YAP1 may reflect the dysregulation of the Hippo pathway in OTSCC, which possibly influences mechanisms of tumor progression and clinical behavior in this carcinoma.