Duncan L M, Deeds J, Cronin F E, Donovan M, Sober A J, Kauffman M, McCarthy J J
Dermatopathology Unit and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
J Clin Oncol. 2001 Jan 15;19(2):568-76. doi: 10.1200/JCO.2001.19.2.568.
Melastatin (MLSN-1), a novel melanocyte-specific gene recently identified using a genomic approach, is expressed in murine and human melanoma cells at levels inversely proportional to metastatic rates in vivo. We studied the relationship between expression of melastatin mRNA in the primary cutaneous tumor and prognosis in patients with localized malignant melanoma.
Melastatin mRNA was evaluated by in situ hybridization in primary cutaneous melanoma from 150 patients with localized disease (American Joint Committee on Cancer [AJCC] stage I and II). Multivariate Cox proportional hazards regression analysis was performed to assess the prognostic utility of melastatin mRNA expression while adjusting for other prognostic indicators.
Uniform melastatin mRNA expression in the primary tumor was correlated with prolonged disease-free survival (P < .0001). Multivariate analysis revealed that melastatin status, mitotic rate, and tumor thickness influence disease-free survival independently. The 8-year disease-free survival rate in AJCC stage I patients whose tumors diffusely expressed melastatin mRNA was 100%, whereas in stage I patients with melastatin loss, the disease-free survival rate was 77% +/- 15% (median +/- SE). In patients with stage II disease whose tumors diffusely expressed melastatin mRNA, the 8-year disease-free survival rate was 90% +/- 7%, whereas in patients with melastatin loss, the disease-free survival rate was 51% +/- 8%.
Downregulation of melastatin mRNA in the primary cutaneous tumor is a prognostic marker for metastasis in patients with localized malignant melanoma and is independent of tumor thickness and other variables. Used in combination, melastatin status and tumor thickness allow for the identification of subgroups of patients at high and low risk of developing metastatic disease.
褪黑素（MLSN-1）是一种最近通过基因组学方法鉴定出的新型黑素细胞特异性基因，在鼠类和人类黑色素瘤细胞中的表达水平与体内转移率呈反比。我们研究了原发性皮肤肿瘤中褪黑素mRNA的表达与局限性恶性黑色素瘤患者预后之间的关系。
通过原位杂交评估了150例局限性疾病患者（美国癌症联合委员会[AJCC] I期和II期）原发性皮肤黑色素瘤中的褪黑素mRNA。进行多变量Cox比例风险回归分析，以评估褪黑素mRNA表达的预后效用，同时对其他预后指标进行校正。
原发性肿瘤中褪黑素mRNA的一致表达与无病生存期延长相关（P <.0001）。多变量分析显示，褪黑素状态、有丝分裂率和肿瘤厚度独立影响无病生存期。AJCC I期患者中，肿瘤弥漫性表达褪黑素mRNA的患者8年无病生存率为100%，而褪黑素缺失的I期患者无病生存率为77%±15%（中位数±标准误）。II期疾病患者中，肿瘤弥漫性表达褪黑素mRNA的患者8年无病生存率为90%±7%，而褪黑素缺失的患者无病生存率为51%±8%。
原发性皮肤肿瘤中褪黑素mRNA的下调是局限性恶性黑色素瘤患者转移的预后标志物，且独立于肿瘤厚度和其他变量。联合使用褪黑素状态和肿瘤厚度可识别发生转移性疾病高风险和低风险的患者亚组。
