Imrédi Eleonóra, Tóth Béla, Doma Viktória, Barbai Tamás, Rásó Erzsébet, Kenessey István, Tímár József
aSecond Department of Pathology, Semmelweis University bDepartment of Dermatology, Venerology and Dermatooncology of Semmelweis University cMolecular Oncology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
Melanoma Res. 2016 Jun;26(3):254-60. doi: 10.1097/CMR.0000000000000243.
Despite experimental findings suggesting the prognostic significance of Aquaporin 1 (AQP1) in human melanoma, no published clinical data are available. We studied the expression of AQP1 protein in cutaneous melanoma, correlated our findings with standard histological and genetic markers, and long-term clinical follow-up. Our study evaluated the AQP1 protein expression in 78 melanoma patients, representing two predefined risk cohorts using the immune labeling technique with commercially available anti-AQP1 antibodies on routinely formalin-fixed and paraffin-embedded tumor tissue samples. BRAF V600E mutation analyses were carried out successfully in 70 patients using PCR and restriction fragment length polymorphism analyses, followed by confirmatory analysis with the Sanger sequencing technique. AQP1-expressing melanoma cells were found in 52 cases (66.7%, median H-score=124.24). Significantly higher AQP1 H-scores (P=0.047) were found in the 'high-risk' patients. No correlations were found with the established histological markers, such as mitotic index (P=0.42), Clark level (P=0.95), and Breslow thickness (P=0.51). BRAF V600 mutation analyses were successful in 89%, and showed a two times higher mutation frequency in the 'high-risk' group. The BRAF V600 mutations were significantly associated with AQP1 expression (P=0.014). Long-term follow-up indicated a reduced progression-free survival (P=0.036) and overall survival (P=0.017) for the AQP1-positive cutaneous melanoma patients. AQP1 expression is likely to be associated with an adverse prognosis in cutaneous melanoma.
尽管实验结果表明水通道蛋白1（AQP1）在人类黑色素瘤中具有预后意义，但尚无已发表的临床数据。我们研究了皮肤黑色素瘤中AQP1蛋白的表达，将我们的研究结果与标准组织学和基因标志物以及长期临床随访进行关联。我们的研究使用市售抗AQP1抗体的免疫标记技术，在常规福尔马林固定和石蜡包埋的肿瘤组织样本上，评估了78例黑色素瘤患者中AQP1蛋白的表达，这些患者代表两个预先定义的风险队列。使用聚合酶链反应（PCR）和限制性片段长度多态性分析，随后用桑格测序技术进行验证分析，成功对70例患者进行了BRAF V600E突变分析。在52例病例（66.7%，中位H评分=124.24）中发现了表达AQP-1的黑色素瘤细胞。在“高危”患者中发现AQP1的H评分显著更高（P=0.047）。未发现与有丝分裂指数（P=0.42）、克拉克分级（P=0.95）和布雷斯洛厚度（P=0.51）等既定组织学标志物存在相关性。BRAF V600突变分析成功率为89%，且在“高危”组中突变频率高出两倍。BRAF V600突变与AQP1表达显著相关（P=0.014）。长期随访表明，AQP1阳性皮肤黑色素瘤患者的无进展生存期（P=0.036）和总生存期（P=0.017）缩短。AQP1表达可能与皮肤黑色素瘤的不良预后相关。
