Subtype-Dependent Expression Patterns of Core Hippo Pathway Components in Thymic Epithelial Tumors (TETs): An RT-qPCR Study

<b>Background/Objectives:</b> Thymic epithelial tumors (TETs) are rare, histologically heterogeneous neoplasms lacking robust molecular biomarkers. Hippo pathway dysregulation-driving <i>YAP</i>/<i>TEAD</i>-dependent transcription-has been implicated across cancers, but transcript-level data in TETs are limited. <b>Methods:</b> We profiled 26 (23 TETs and three normal thymus) formalin-fixed and paraffin-embedded (FFPE) specimens by SYBR real-time quantitative polymerase chain reaction (RT-qPCR) across World Health Organization (WHO) subtypes, focusing on core Hippo components <i>YAP1</i>, <i>TEAD4</i>, <i>MST1</i>, <i>SAV1</i>, <i>LATS1</i>, and <i>MOB1A</i>. Expression was normalized to the geometric mean of <i>HPRT1</i> and <i>TBP</i> and reported as log₂ fold change (log₂FC) using the 2^-ΔΔCq method relative to the pooled normal. Group differences were compared using non-parametric tests. <b>Results:</b> Median log₂FC values showed subtype-dependent upregulation of <i>YAP1</i>/<i>TEAD4</i>, notably in type A (<i>YAP1</i> ≈ +3.43) and B3 (<i>YAP1</i> ≈ +2.78) thymomas, with <i>TEAD4</i> strongly increased in thymic carcinoma (TC; ≈ +3.49) and elevated in type A/B3. Upstream kinases tended to be subtype-specifically reduced, particularly in TC (<i>MST1</i> ≈ -1.38; <i>LATS1</i> ≈ -1.34), and modestly in B1. <i>SAV1</i> was elevated in type A (≈+2.25) and B3 (≈+2.01), while <i>MOB1A</i> remained near baseline. Differential expression among WHO subtypes (Kruskal-Wallis) was significant for <i>YAP1</i> (<i>p</i> = 0.003), <i>TEAD4</i> (<i>p</i> = 0.015), <i>SAV1</i> (<i>p</i> = 0.004), <i>MST1</i> (<i>p</i> = 0.012), and <i>LATS1</i> (<i>p</i> = 0.036), but not for <i>MOB1A</i> (<i>p</i> = 0.09). <b>Conclusions:</b> TETs seem to exhibit subtype-dependent expression patterns of core Hippo pathway components, characterized by enhanced <i>YAP1</i>-<i>TEAD4</i> transcriptional output in selected subtypes and marked reduction of the <i>MST1</i>/<i>LATS1</i> kinase module, most pronounced in TC. These exploratory patterns nominate candidate markers for subtype stratification and clinical validation.