Abstract:

Wen Sijian, Ni Nana, Zhang Wei, Song Hao, Wang Xiaopo, Shao Xuebao, Li Amei, Cheng Wei, Sun Jianfang Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China （Wen SJ, Zhang W, Song H, Wang XP, Shao XB, Li AM, Cheng W, Sun JF）; Central Laboratory, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China （Ni NN） Corresponding authors: Sun Jianfang, Email: fangmin5758@aliyun.com; Zhang Wei, Email: ifmtjoel@163.com 【Abstract】 Objective To measure histidine triad nucleotide?binding protein 1 （HINT1） protein and gene promoter methylation, and to analyze the relationship between HINT1 gene promoter methylation and clinical pathological features of melanoma. Methods Fifty?six patients with melanoma and 51 patients with nevus were enrolled as subjects and controls, respectively. Methylation?specific PCR （MSP） was performed to measure the methylation of HINT1 gene promoter in lesional and paratumoral tissue specimens from the patients with melanoma, as well as in lesional specimens from the patients with nevus. Immunohistochemistry was carried out to quantify the of HINT1 protein in these tissue specimens. Results MSP showed that the methylation rate of HINT1 gene promoter was significantly higher in melanoma tissues than in paratumoral and nevus tissues（76.8% ［43/56］ vs. 33.9%［19/56］ and 35.3%［18/51］, χ2 = 20.810 and 18.749, respectively, both P < 0.05）, but was insignificantly different between paratumoral and nevus tissues （χ2 = 0.022, P > 0.05）. Immunohistochemistry revealed that the rate of HINT1 was 21.4% （12/56） in melanoma tissues, compared to 82.4% （42/51） in nevus tissues （χ2 = 39.633, P < 0.01）. There was a significant difference in the methylation rate of HINT1 promoter between HINT1?positive and ?negative melanoma tissues （6/12 vs. 37/44 ［84.1%］, P < 0.05）, and between Clark level Ⅰ-Ⅱ and Ⅲ-Ⅴ melanoma tissues （59.1% ［13/22］ vs. 88.2% ［30/34］, χ2 = 6.365，P = 0.012）. Conclusions HINT1 protein is lowly expressed in melanoma, which may be associated with high methylation of its gene promoter. Moreover, the high methylation of HINT1 gene promoter may be involved in the initiation and progression of melanoma.