Clinicopathological and Molecular Characterization of Papillary Thyroid Carcinoma in a Saudi Arabian Cohort: An Integrated Analysis

Abstract

Background: The rising incidence of Papillary Thyroid Carcinoma (PTC) in Saudi Arabia necessitates a deeper understanding of the factors driving aggressive disease. This study aimed to evaluate the prognostic significance of KRAS mutations and a standard immunohistochemical (IHC) panel in PTC within a Saudi cohort. Methods: A retrospective cohort study of 150 PTC cases from a major Saudi tertiary care center was performed. Associations between clinicopathological parameters, IHC expression profiles (CK19, HBME-1, Galectin-3, TTF-1, Ki67), and KRAS mutational status with lymph node metastasis (LNM) and extrathyroidal extension (ETE) were analyzed using Chi-square tests, Fisher’s exact tests, t-tests, and multivariate logistic regression. Results: The cohort demonstrated high rates of LNM (46.0%) and ETE (36.0%). KRAS mutations were identified in 11.3% of cases. No statistically significant association was found between KRAS status and LNM (p=1.000) or ETE (p=0.460). The evaluated IHC markers did not correlate significantly with LNM. A non-significant trend linked aggressive variants (Tall Cell and Solid) with higher LNM frequency compared to non-aggressive variants (58.8% vs. 42.3%; p=0.117). Multivariate logistic regression identified aggressive variant morphology as the strongest trend toward predicting LNM (OR=2.08, 95% CI: 0.93–4.69, p=0.076), without reaching significance. Conclusions: In this Saudi cohort, KRAS mutations and the evaluated IHC panel did not serve as significant predictors of aggressive PTC behavior. Morphological assessment remains paramount for risk stratification, and larger population-specific studies are needed to identify robust prognostic biomarkers.