Nikolaos G Nikitakis1, George Z Rassidakis2, Jason Tasoulas3, Ioannis Gkouveris4, Georgios Kamperos5, Argyrios Daskalopoulos5, Alexandra Sklavounou5. 1. Department of Oral Medicine and Pathology, School of Dentistry, National and Kapodistrian University of Athens, Greece. Electronic address: Nnikitakis1@yahoo.com. 2. Karolinska Institutet, Stockholm, Sweden. 3. First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Greece. 4. Department of Oral Medicine and Pathology, School of Dentistry, National and Kapodistrian University of Athens, Greece; Division of Diagnostics and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA, USA. 5. Department of Oral Medicine and Pathology, School of Dentistry, National and Kapodistrian University of Athens, Greece.
Abstract
OBJECTIVES: The aim of this study was to evaluate the expression levels of DNA damage response (DDR) markers in potentially preneoplastic oral epithelial lesions (PPOELs). STUDY DESIGN: Immunohistochemical expression of DDR markers (γΗ2 ΑΧ, pChk2, 53 BP1, p53, and phosphorylated at Ser 15 p53) was assessed in 41 oral leukoplakias, ranging from hyperplasia (H) to dysplasia (D) and in comparison with oral squamous cell carcinoma (OSCC) and normal mucosa (NM). Statistical and receiver operating characteristic curve analysis were performed. RESULTS: γH2 AX 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. 53 BP1 demonstrated higher levels in OSCC than in NM, whereas 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. CONCLUSIONS: DDR 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.
OBJECTIVES: The aim of this study was to evaluate the expression levels of DNA damage response (DDR) markers in potentially preneoplastic oral epithelial lesions (PPOELs). STUDY DESIGN: Immunohistochemical expression of DDR markers (γΗ2 ΑΧ, pChk2, 53 BP1, p53, and phosphorylated at Ser 15 p53) was assessed in 41 oral leukoplakias, ranging from hyperplasia (H) to dysplasia (D) and in comparison with oral squamous cell carcinoma (OSCC) and normal mucosa (NM). Statistical and receiver operating characteristic curve analysis were performed. RESULTS: γH2 AX 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. 53 BP1 demonstrated higher levels in OSCC than in NM, whereas 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. CONCLUSIONS: DDR 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.