Siroy Alan E, Aung Phyu P, Torres-Cabala Carlos A, Tetzlaff Michael T, Nagarajan Priyadharsini, Milton Denái R, Curry Jonathan L, Ivan Doina, Prieto Victor G
Department of Pathology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030.
Department of Pathology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030; Department of Dermatology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030.
Hum Pathol. 2017 Jan;59:48-54. doi: 10.1016/j.humpath.2016.09.010. Epub 2016 Sep 22.
Capsular nevi (CN) are clusters of benign melanocytes situated in the capsule of lymph nodes and occur in up to 20% of lympadenectomy specimens. The molecular profile of CN in relation to prognostic parameters in patients with primary cutaneous melanoma (PCM) has not been previously investigated. We assessed BRAF V600E mutation by immunohistochemistry (IHC) in the CN of sentinel lymph nodes (SLN) in PCM patients and correlated the findings with demographic characteristics, PCM histopathologic and molecular features, and clinical outcome parameters. Seventy-eight cases of CN involving SLN of PCM patients were evaluated for BRAF V600E mutation by IHC. The results were correlated with patient demographics, PCM histopathologic and molecular features, and outcome measures. Thirty-six (46%) of 78 CN cases expressed BRAF V600E mutation by IHC. Nineteen (53%) of those BRAF-positive CN cases were from patients with at least American Joint Committee on Cancer stage II melanoma, whereas 62% of BRAF-negative CN cases (26/42) were from patients with stage I melanoma (P = .013). Twelve (33%) of the 36 BRAF-positive CN cases had metastatic melanoma involving lymph nodes, compared with 14% (6/42) of BRAF-negative CN cases (P = .061). CN mutation status was not associated with patient demographics, histopathologic or molecular features of the PCM, or survival outcomes. A high percentage of CN identified in the SLN of patients with PCM harbor BRAF V600E mutation. Positive mutation was associated with adverse clinicopathological parameters, specifically increased tumor stage and lymph node metastasis. These findings suggest that BRAF V600E mutation in CN of SLN may be useful as an adverse predictive biomarker in patients with melanoma.
包膜痣(CN)是位于淋巴结包膜内的良性黑素细胞簇,在高达20%的淋巴结切除标本中出现。此前尚未研究过CN与原发性皮肤黑色素瘤(PCM)患者预后参数相关的分子特征。我们通过免疫组织化学(IHC)评估了PCM患者前哨淋巴结(SLN)中CN的BRAF V600E突变情况,并将结果与人口统计学特征、PCM组织病理学和分子特征以及临床结局参数进行关联。通过IHC对78例涉及PCM患者SLN的CN病例进行BRAF V600E突变评估。将结果与患者人口统计学、PCM组织病理学和分子特征以及结局指标进行关联。78例CN病例中有36例(46%)通过IHC检测出BRAF V600E突变。其中19例(53%)BRAF阳性的CN病例来自至少处于美国癌症联合委员会II期黑色素瘤的患者,而BRAF阴性的CN病例中有62%(26/42)来自I期黑色素瘤患者(P = 0.013)。36例BRAF阳性的CN病例中有12例(33%)发生了累及淋巴结的转移性黑色素瘤,相比之下,BRAF阴性的CN病例中有14%(6/42)发生了这种情况(P = 0.061)。CN突变状态与患者人口统计学、PCM的组织病理学或分子特征以及生存结局无关。在PCM患者的SLN中发现的CN有很大比例存在BRAF V600E突变。阳性突变与不良的临床病理参数相关,特别是肿瘤分期增加和淋巴结转移。这些发现表明,SLN的CN中的BRAF V600E突变可能作为黑色素瘤患者的不良预测生物标志物。