The Expression Of HERG1,K_V 3.4 In Oral Lichen Planus And Oral Squamous Cell Carcinoma

Objective:Oral lichen planus (OLP) is the most common disease in the oral mucosa.It usually takes place in bucca,mouth bottom and tongue etc.It has a certain malignant transformation rate which is identified by the World Health Organization (WHO) as a precancerous condition. Oral squamous cell carcinoma (OSCC) is the most common oral cancer developed mostly from oral precancerous lesion or precancerous condition. The early diagnosis and treatment of precancerous lesions and precancerous conditions are contributed to the prevention of the OSCC.Potassium channels and currents play important roles in many physiological functions.Recent studies indicated that some potassium channels were associated with carcinogenesis.Some researchers had focused on the relationship between voltage-gated potassium channel and tumor.Human ether-a-go-go-related gene(herg) encoding a subunit of delayed rectifier potassium channel has been indicated with involvement in tumor cell growth and death. Recent studies indicated that HERG1 and KV3.4 potassium channels were more frequently expressed in cancer as compared to non-cancer. This study is planned to examine the expression of HERG1 and KV3.4 in normal oral mucosa, oral lichen planus, and oral squamous cell carcinoma by immumohistochemistry(IHC) and to investigate the expression pattern of HERG1 and KV3.4 during the development and progression of OSCC. Methods:20 OLP specimens who did not undergo any treatment were collected, including 11 cases of erosive OLP and 9 cases of non-erosive type.30 OSCC surgical resection specimens who did not undergo chemical and radiative treatment were collected, graded according to the WHO standard for OSCC histological grading. Gingival tissues from removing impacted tooth and tissues around the benign lesions of 16 cases were set as control group. The tissues were fixed with 4% neutral formalin for 24 hours, embedded with paraffin, cut into 4μm thick serial sections and immunohistochemically stained with SP methods using rabbit anti-human ether-a-go-go-related gene (herg1), Voltage gated potassium channel subunit KV3.4 (Bioworld).The positive staining showed as brown-yellow in cytoplasm or membrane. According to staining intensity and number of positive cells, the staining were divided into-,+,++ and+++. Each index in the normal epithelium, OLP tissue, OSCC tissue was compared with two sample rank test methods. Expressions of HERG1 and KV3.4 in the cancer were analyzed by Spearman correlation analysis. Statistical analysis was completed by SPSS 16.0 statistical software. Results: 1.HERG1 expressed negatively or weakly positively in basal layer of NOM and non-erosive OLP, but showed as positive in basal layer, spinous layer and granular layer of erosive OLP. Expression of HERG1 was positive to strong staining in OSCC cancer cells. Strong staining distributed mainly in well-differentiated areas,particularly in well differentiated keratinizing cells. Expression of HERG1 was higher in OLP and OSCC than NOM tissues, P=0.000(P<0.05). The better OSCC differentiated, the stronger HERG1 expressed; the poorer OSCC differentiated, the weaker HERG1 expressed, P=0.041(P<0.05).Expression of HERG1 is higher in erosive OLP than non-erosive OLP, P=0.025(P＜0.05).2. KV3.4 expressed negatively or weakly positively in basal layer of NOM and non-erosive OLP, but showed as positive to intensive expression in basal layer, spinous layer and granular layer of erosive OLP. Expression of KV3.4 was positive to intensive staining in OSCC cancer cells. Intensive staining distributed mainly in well-differentiated areas, particularly in well differentiated keratinizing cells. Expression of KV3.4 was higher in OSCC than in NOM tissues, P=0.006(P＜0.05), the difference was significant. Expression of KV3.4 was higher in erosive OLP than non-erosive OLP, P=0.025(P<0.05).3. Expressions of HERG1 and KV3.4 were positive immunostaining in vascular endothelial cell,acinus and muscularis externa,but negligible immunostaining in stromal cells.4.The expression of HERG1 and KV3.4 in OLP tissue had tight correlation, r=0.655,P=0.002 (P＜0.05).5. The expression of HERG1 and KV3.4 in OSCC tissue has tight correlation, r=0.828, p=0.000 (P＜0.05). Conclusion:1. Expressions of HERG1 and KV3.4 are higher in OLP and OSCC than NOM tissues, which may be related to the cancerization of oral mucosa.2. The expression of HERG1 is different apparently in well differentiated,moderately differentiated and poorly differentiated, which may be related to the difference of OSCC.3. Expressions of HERG1 and KV3.4 in OLP and OSCC are well correlated. Therefore, their combined applicaton may be provide new diagnostic markers and therapeutic targets for clinical diagnosis and treatment of OLP and OSCC.