Abstract：
OBJECTIVE: To identify high-risk histopathologic and molecular features of local recurrence, nodal metastasis, distant metastasis (DM) and disease-specific death (DSD) in conjunctival melanoma (CoM).
METHODS: Ninety patients with pathologically diagnosed CoM between 2008 and 2023 were enrolled. Immunohistochemistry staining of BRAFV600E , NRASQ61R , CD117, PD-1 and PD-L1 was performed in 65 and 45 patients, respectively. Cox regression and Kaplan-Meier survival analysis were conducted to identify risk factors for local recurrence, nodal metastasis, DM and DSD.
RESULTS: Pathologically, ulceration (hazard ratio [HR]: 3.170; 95% CI: 1.312-7.659; p = 0.01) and regression (HR: 3.196; 95% CI: 1.094-9.335; p = 0.034) were risk factors for DM. Tumour thickness ≥ 4 mm (HR: 4.889; 95% CI: 1.846-12.946; p = 0.001) and regression (HR: 4.011; 95% CI: 1.464-10.991; p = 0.007) were risk factors for DSD. For patients with tumour thickness < 4 mm, the presence of ulceration indicated a higher risk of nodal metastasis (log-rank p = 0.0011), DM (log-rank p = 0.00051) and DSD (log-rank p = 0.02). Patients with regression (+)/tumour-infiltrating lymphocytes (TILs) (+) had a higher risk for DM (log-rank p = 0.011) and DSD (log-rank p = 0.0032). Molecularly, the positive rate of BRAFV600E , NRASQ61R , CD117, PD-1 and PD-L1 was 40.00% (26/65), 43.08% (28/65), 70.77% (46/65), 46.67% (21/45) and 28.89% (13/45), respectively. Positive BRAFV600E was identified as an independent risk factor for DM (HR: 2.533; 95% CI: 1.046-6.136, p = 0.039). The expression level of BRAFV600E was positively correlated with vascular invasion (p = 0.01), as well as the expression levels of PD-1 (p = 0.038) and PD-L1 (p = 0.049).
CONCLUSIONS: Tumour thickness ≥ 4 mm, ulceration, the coexistence of regression and TILs, and positive BRAFV600E were risk factors for poor prognosis of CoM patients. Besides, expression level of BRAFV600E was positively correlated with the expression levels of PD-1 and PD-L1.
METHODS: Ninety patients with pathologically diagnosed CoM between 2008 and 2023 were enrolled. Immunohistochemistry staining of BRAFV600E , NRASQ61R , CD117, PD-1 and PD-L1 was performed in 65 and 45 patients, respectively. Cox regression and Kaplan-Meier survival analysis were conducted to identify risk factors for local recurrence, nodal metastasis, DM and DSD.
RESULTS: Pathologically, ulceration (hazard ratio [HR]: 3.170; 95% CI: 1.312-7.659; p = 0.01) and regression (HR: 3.196; 95% CI: 1.094-9.335; p = 0.034) were risk factors for DM. Tumour thickness ≥ 4 mm (HR: 4.889; 95% CI: 1.846-12.946; p = 0.001) and regression (HR: 4.011; 95% CI: 1.464-10.991; p = 0.007) were risk factors for DSD. For patients with tumour thickness < 4 mm, the presence of ulceration indicated a higher risk of nodal metastasis (log-rank p = 0.0011), DM (log-rank p = 0.00051) and DSD (log-rank p = 0.02). Patients with regression (+)/tumour-infiltrating lymphocytes (TILs) (+) had a higher risk for DM (log-rank p = 0.011) and DSD (log-rank p = 0.0032). Molecularly, the positive rate of BRAFV600E , NRASQ61R , CD117, PD-1 and PD-L1 was 40.00% (26/65), 43.08% (28/65), 70.77% (46/65), 46.67% (21/45) and 28.89% (13/45), respectively. Positive BRAFV600E was identified as an independent risk factor for DM (HR: 2.533; 95% CI: 1.046-6.136, p = 0.039). The expression level of BRAFV600E was positively correlated with vascular invasion (p = 0.01), as well as the expression levels of PD-1 (p = 0.038) and PD-L1 (p = 0.049).
CONCLUSIONS: Tumour thickness ≥ 4 mm, ulceration, the coexistence of regression and TILs, and positive BRAFV600E were risk factors for poor prognosis of CoM patients. Besides, expression level of BRAFV600E was positively correlated with the expression levels of PD-1 and PD-L1.
摘要：
目的：确定局部复发的高危组织病理学和分子学特征，淋巴结转移,结膜黑色素瘤（CoM）的远处转移（DM）和疾病特异性死亡（DSD）。
方法：纳入2008年至2023年90例经病理诊断为CoM的患者。BRAFV600E的免疫组织化学染色，NRASQ61R,CD117，PD-1和PD-L1分别在65和45例患者中进行，分别。进行Cox回归和Kaplan-Meier生存分析以确定局部复发的危险因素。淋巴结转移,DM和DSD。
结果：病理，溃疡(风险比[HR]:3.170;95%CI:1.312-7.659;p=0.01)和回归(HR:3.196;95%CI:1.094-9.335;p=0.034)是DM的危险因素。肿瘤厚度≥4mm(HR:4.889;95%CI:1.846-12.946;p=0.001)和消退(HR:4.011;95%CI:1.464-10.991;p=0.007)是DSD的危险因素。对于肿瘤厚度<4mm的患者，溃疡的存在表明淋巴结转移的风险较高（log-rankp=0.0011），DM(对数秩p=0.00051)和DSD(对数秩p=0.02)。回归（）/肿瘤浸润淋巴细胞（TIL）（）的患者患DM（log-rankp=0.011）和DSD（log-rankp=0.0032）的风险较高。分子上，BRAFV600E阳性率,NRASQ61R,CD117、PD-1和PD-L1为40.00%(26/65)，43.08%（28/65），70.77%（46/65），46.67%（21/45）和28.89%（13/45），分别。BRAFV600E阳性被确定为DM的独立危险因素(HR:2.533;95%CI:1.046-6.136,p=0.039)。BRAFV600E的表达水平与血管侵犯呈正相关(p=0.01),以及PD-1（p=0.038）和PD-L1（p=0.049）的表达水平。
结论：肿瘤厚度≥4mm，溃疡,回归和TIL的共存，BRAFV600E阳性是CoM患者预后不良的危险因素。此外,BRAFV600E的表达水平与PD-1和PD-L1的表达水平呈正相关。
方法：纳入2008年至2023年90例经病理诊断为CoM的患者。BRAFV600E的免疫组织化学染色，NRASQ61R,CD117，PD-1和PD-L1分别在65和45例患者中进行，分别。进行Cox回归和Kaplan-Meier生存分析以确定局部复发的危险因素。淋巴结转移,DM和DSD。
结果：病理，溃疡(风险比[HR]:3.170;95%CI:1.312-7.659;p=0.01)和回归(HR:3.196;95%CI:1.094-9.335;p=0.034)是DM的危险因素。肿瘤厚度≥4mm(HR:4.889;95%CI:1.846-12.946;p=0.001)和消退(HR:4.011;95%CI:1.464-10.991;p=0.007)是DSD的危险因素。对于肿瘤厚度<4mm的患者，溃疡的存在表明淋巴结转移的风险较高（log-rankp=0.0011），DM(对数秩p=0.00051)和DSD(对数秩p=0.02)。回归（）/肿瘤浸润淋巴细胞（TIL）（）的患者患DM（log-rankp=0.011）和DSD（log-rankp=0.0032）的风险较高。分子上，BRAFV600E阳性率,NRASQ61R,CD117、PD-1和PD-L1为40.00%(26/65)，43.08%（28/65），70.77%（46/65），46.67%（21/45）和28.89%（13/45），分别。BRAFV600E阳性被确定为DM的独立危险因素(HR:2.533;95%CI:1.046-6.136,p=0.039)。BRAFV600E的表达水平与血管侵犯呈正相关(p=0.01),以及PD-1（p=0.038）和PD-L1（p=0.049）的表达水平。
结论：肿瘤厚度≥4mm，溃疡,回归和TIL的共存，BRAFV600E阳性是CoM患者预后不良的危险因素。此外,BRAFV600E的表达水平与PD-1和PD-L1的表达水平呈正相关。
