HINT1 protein expression and gene promoter methylation in melanoma tissue

Objective To measure histidine triad nucleotide-binding protein 1 (HINT1)protein expression 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 expression 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). Immunohistochemistry revealed that the expression 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. Key words: Melanoma; Methylation; Nevus, pigmented; Gene, HINT1