66 例晚期黑色素瘤患者组织中磷酸化成视网膜细胞瘤蛋白表达水平分析及其临床意义评价

摘要] 目的：分析晚期黑色素瘤组织中磷酸化成视网膜细胞瘤蛋白（phosphorylated retinoblastoma，p-Rb）的表达情况，并探讨其与临床病理特征及预后之间的相关性。方法：收集2011 至2014 年在北京大学肿瘤医院肾癌黑色素瘤科住院治疗并符合纳入和排除标准的66 例晚期黑色素瘤患者的临床资料及其石蜡包埋组织切片，采用免疫组化方法检测患者原发灶肿瘤组织中p-Rb 的表达情况，结合患者临床病理特征、总生存期等临床数据进行相关性分析。结果：晚期黑色素瘤组织中p-Rb 的阳性表达率为57.6%(38/66)。非肢端的皮肤型、肢端型及黏膜型的p-Rb阳性率分别为73.7%（14/19）、63.0%（17/27）和35.0%（7/20），差异有统计学意义（P=0.039）。p-Rb 在不同基因突变亚组中的阳性率亦不同，BRAF突变组为83.3%（5/6），C-KIT 突变组为100.0%（2/2），N-RAS突变组为100.0%(9/9)，PDGFRA突变组为50.0%（1/2），2 个基因突变组为50.0%（1/2），基因野生型为44.4%（20/45），差异有统计学意义（P=0.004）。p-Rb表达水平与年龄、性别、分期、溃疡、血清LDH水平无相关性（P>0.05)。p-Rb 阳性患者的中位总生存期（OS）较阴性患者略短（30.0 vs 39.2 个月），但差异无统计学意义（P=0.555）。结论：超过半数的晚期黑色素瘤组织中有p-Rb 的阳性表达，非肢端的皮肤型中p-Rb阳性率高于肢端型、黏膜型，且携带c-KIT 和N-RAS突变的患者黑色素瘤组织中p-Rb阳性率较高。

Expression level and clinical significance of phosphorylated retinoblastoma in tissues of advanced malignant melanoma: An analysis of 66 cases

Abstract] Objective: To investigate the expression of phosphorylated retinoblastoma (p-Rb) in advanced melanoma tissues and to analyze its correlation with clinical pathological characteristics and prognosis. Methods: The clinical data and paraffin-embedded tissue sections of 66 patients with advanced melanoma, who were diagnosed and treated in the Department of Renal Cancer and Melanoma of Peking University Cancer Hospital from 2011 to 2014, were collected. Expression of p-Rb in primary tumor tissues was detected by immunohistochemistry.Correlation analysis was performed on the relationship between the expression level of p-Rb in tumor tissues and clinical data such as clinicopathological features and overall survival. Results: The positive expression rate of p-Rb in advanced melanoma tissues was 57.6% (38/66). The positive rates of p-Rb in non-acral cutaneous type, acral type and mucosal type were 73.7% (14/19), 63.0% (17/27) and 35.0% (7/20), respectively, and the difference was statistically significant (P=0.039). The positive rate of p-Rb in different gene mutation subgroups was also different, with 83.3% (5/6) in the BRAF mutation group, 100.0% (2/2) in the c-KIT mutation group, and 100.0% in the N-RAS mutation group (9/9), 50.0% (1/2) in the PDGFRA mutation group, and 50.0% (1/2) in group with 2-gene mutation, and 44.4% (20/45) in the wild type gene group, and the difference was statistically significant (P=0.004). There was no correlation between p-Rb expression levels and age, gender, stage, ulcer, and serum LDH levels. The median overall survival (OS) of patients with positive p-Rb expression was slightly shorter than that of the patients with negative expression (30.0 vs 39.2 months), but the difference was not statistically significant (P=0.555). Conclusion: More than half of the advanced melanoma tissues have positive expression of p-Rb, and the positive rate of p-Rb in non-acral cutaneous type is higher than that of acral and mucosal types. And the positive rate of p-Rb in melanoma tissues of patients carrying c-KIT and N-RAS mutations is higher.