The Expression of PD-L1, BRAFV600E, CD68 Protein and the Significance of Tumor Infiltrating Lymphocytes in the Diagnosis of Malignant Melanoma
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摘要:
目的 分析PD-L1、BRAFV600E、CD68蛋白和肿瘤浸润淋巴细胞（TIL）在恶性黑色素瘤诊断中的意义。 方法 应用高通量组织芯片技术及免疫组化方法，检测60例原发性恶性黑色素瘤组织中PD-L1、BRAFV600E、CD68蛋白表达；分析PD-L1、BRAFV600E、CD68蛋白以及TIL与患者的临床病理特征及预后关系。 结果 （1）恶性黑色素瘤组织中CD68蛋白表达与肿瘤T分期之间，差异有统计学意义（P = 0.018），而与肿瘤大小、肿瘤浸润深度、淋巴结转移和溃疡形成之间，差异均无统计学意义（P > 0.05）；（2）PD-L1、BRAFV600E和TIL与肿瘤T分期、肿瘤大小、肿瘤浸润深度、淋巴结转移和溃疡形成之间，差异均无统计学意义（P > 0.05）；（3）皮肤黑色素瘤BRAFV600E突变率约36.67%（22/60），其中，肢端型黑色素瘤BRAFV600E突变率约68.18%（15/22）；黏膜黑色素瘤BRAFV600E突变率约23.33%（14/60）；（4）Cox回归生存分析结果显示肿瘤淋巴结转移是影响恶性黑色素瘤患者预后的因素。 结论 （1）CD68蛋白表达在判定患者预后方面可能有一定作用；（2）皮肤部位的黑色素瘤建议行BRAFV600E免疫组化检测；（3）患者存在淋巴结转移可作为恶性黑色素瘤预后判断的参考指标。 Abstract:Objective To analyze the significance of PD-L1, BRAFV600E, CD68 protein expressions and tumor infiltrating lymphocytes （TIL） in the diagnosis of malignant melanoma. Methods High-throughput tissue microarray technology and immunohistochemical methods were used to detect the expressions of PD-L1, BRAFV600E and CD68 in 60 primary malignant melanoma tissues. The relationship between PD-L1, BRAFV600E, CD68 expressions, TIL and the clinicopathological characteristics and prognosis of patients was analyzed. Results （1） There was a statistically significant difference between CD68 expression in malignant melanoma tissue and tumor T stage （P = 0.018）, but no statistical difference between tumor size, tumor invasion depth, lymph node metastasis and ulceration （P > 0.05）. （2） There was no significant difference between PD-L1, BRAFV600E, TIL and tumor T stage, tumor size, tumor invasion depth, lymph node metastasis and ulceration （P > 0.05）. （3） The mutation rate of BRAFV600E in cutaneous melanoma was about 36.67% （22/60）. The mutation rate of BRAFV600E in cutaneous acral melanoma was about 68.18%. （15/22）. The mutation rate of BRAFV600E in mucosal melanoma was about 23.33% （14/60）. （4） Cox regression analysis showed that lymph node metastasis was the prognostic factor of malignant melanoma patients. Conclusion （1） The expression of CD68 protein may play a role in determining the prognosis of patients. （2） BRAFV600E immunohistochemical detection is recommended for melanoma in the skin. （3） The presence of lymph node metastasis in patients can be used as a reference index for the prognosis of malignant melanoma. -
Key words:
- Malignant Melanoma /
- PD-L1 /
- BRAFV600E /
- CD68 /
- TIL /
- Immunohistochemistry
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图 1 恶性黑色素瘤PD-L1蛋白强阳性表达（SP × 200）
Figure 1. The strong positive expression of PD-L1 protein in malignant melanoma （SP × 200）
图 2 恶性黑色素瘤BRAFV600E 蛋白阳性表达（SP × 200）
Figure 2. The positive expression of BRAFV600E protein in malignant melanoma （SP × 200）
图 3 恶性黑色素瘤细胞CD68蛋白阳性表达（SP × 200）
Figure 3. The strong positive expression of CD68 protein in malignant melanoma （SP × 200）
图 4 恶性黑色素瘤组织中少量淋巴细胞浸润 （HE × 200）
Figure 4. A few lymphocytes infiltrated in the malignant melanoma （HE × 200）
图 5 恶性黑色素瘤组织中大量淋巴细胞浸润 （HE×200）
Figure 5. With extensive lymphocytes infiltrated in the malignant melanoma （HE × 200）
表 1 多因素 COX比例风险回归模型
Table 1. Multivariate COX proportional hazards regression model
影响因素 β SE Wald P RR 95%CI 转移 0.926 0.451 4.225 0.040 2.524 1.044～6.105 
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