This study aimed to evaluate the expression levels of hypoxia-inducible factor 1-α (HIF-1α) and vascular endothelial growth factor (VEGF) in radicular cysts and periapical granulomas, thereby contributing to the understanding of their potential significance in the differential diagnosis and treatment of these lesions. In the present cross-sectional study, 51 samples of periapical lesions were included. Of them, 24 samples were radicular cysts, and 27 samples were periapical granulomas. Samples were immunohistochemically analyzed for HIF-1α and VEGF proteins expression. Chi-square tests and Spearman's rank correlation coefficient tests were used to detect differences and correlations among the parameters, respectively. In radicular cysts, HIF-1α expression was absent in 1 (4.2%), weak in 5 (20.8%), mild in 7 (29.2%), and strong in 11 (45.8%) cases, while VEGF expression was absent in 1 (4.2%), weak in 6 (25.0%), mild in 9 (37.5%), and strong in 8 (33.3%) of the cases; nevertheless, in periapical granulomas, HIF-1α expression was absent in 8 (29.6%), weak in 6 (22.2%), mild in 9 (33.3%), and strong in 4 (14.8%) of the cases, whereas VEGF expression was absent in 4 (14.8%), weak in 16 (59.3%), mild in 4 (14.8%), and strong in 3 (11.1%) of the cases. Chi-square test revealed a significant difference in the expression of HIF-1α and VEGF between radicular cysts and periapical granuloma (chi-square test = 8.906, p = 0.031; chi-square test = 10.401, p = 0.015, respectively). Spearman's correlation test showed a significant correlation between HIF-1α and VEGF in the total samples of both radicular cysts and periapical granulomas (rho = 0.385, p = 0.005). There is high expression of both HIF-1α and VEGF throughout the odontogenic epithelium and connective tissue of the radicular cyst and periapical granuloma. Both HIF-1α and VEGF are more highly expressed in radicular cysts than in periapical granulomas. These findings may aid in the diagnosis and management of suspected periapical lesions, suggesting that radicular cysts exhibit more advanced hypoxic conditions and associated pathways compared with periapical granulomas.
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