LMTK3 as a spatially regulated and stage-dependent biomarker in epithelial ovarian tumorigenesis

Lemur tyrosine kinase 3 (LMTK3) has been implicated in cancer prognosis and progression. While its role in early-stage epithelial ovarian cancer (EOC) has been explored, the dynamics of its subcellular expression across the disease spectrum remain unclear. LMTK3 protein expression was assessed by immunohistochemistry on tissue microarrays comprising benign, borderline, and malignant ovarian tumors (n = 532). Nuclear and cytoplasmic staining were quantified via histochemical scores (H-scores) and analyzed in relation to histotype, disease stage, and overall survival. LMTK3 was broadly expressed across all tumor types, with predominant nuclear localization in benign and borderline lesions. Malignant tumors exhibited increased cytoplasmic expression and a stronger nuclear-cytoplasmic correlation (ρ = 0.73, p < 0.001), indicating altered spatial regulation during tumor progression. Within malignant EOC, LMTK3 expression patterns varied significantly by histotype and disease stage, reflecting context-dependent subcellular regulation. High nuclear expression was associated with better survival in early-stage EOC (adj. hazard ratio [HR] 0.33, p < 0.001), while cytoplasmic dominance suggested a favorable outcome in advanced-stage cases in multivariable analysis (HR = 0.53, p = 0.047). LMTK3 expression and subcellular localization evolve during ovarian tumorigenesis. These patterns carry stage-specific prognostic implications, supporting LMTK3 as a spatially resolved biomarker for EOC stratification.