Alterations in the expression of DNA damage response-related molecules in potentially preneoplastic oral epithelial lesions

Publication date: Available online 22 March 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Nikolaos G. Nikitakis, George Z. Rassidakis, Jason Tasoulas, Ioannis Gkouveris, Georgios Kamperos, Argyrios Daskalopoulos, Alexandra Sklavounou
ObjectivesTo evaluate the expression levels of DNA damage response (DDR) markers in potentially preneoplastic oral epithelial lesions (PPOELs).Study designImmunohistochemical expression of DDR markers (γΗ2ΑΧ, pChk2, 53BP1, p53 and phosphorylated at Ser 15 p53) was assessed in 41 oral leukoplakias ranging from hyperplasia (H) to dysplasia (D), and compared with oral squamous cell carcinoma (OSCC) and normal mucosa (NM). Statistical and ROC curve analysis were performed.ResultsγH2AX immunoexpression demonstrated a gradual increase and upper layer extension from NM to H to higher D degrees to OSCC. pChk2 expression was minimal in NM, relatively low in PPOELs with an increasing tendency from H to D, and higher in OSCC. 53BP1 demonstrated higher levels in OSCC than NM, while its expression in PPOELs was heterogeneous, gradually increasing according to D. p53 demonstrated progressively higher levels and upper layer extension from H to D to OSCC. Phosphorylated p53 was absent in NM and relatively low in PPOELs and OSCC.ConclusionsDDR markers' expression is variable in PPOELs showing a tendency to increase along with dysplasia. Activated DDR mechanisms may play an important protective role at early stages of oral carcinogenesis, but probably suffer progressive deregulation, eventually failing to suppress malignant transformation.



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