Spathis Aris, Katoulis Alexander C, Damaskou Vasileia, Liakou Aikaterini I, Kottaridi Christine, Leventakou Danai, Sgouros Dimitrios, Mamantopoulos Andreas, Rigopoulos Dimitrios, Karakitsos Petros, Panayiotides Ioannis G
Second Department of Pathology, National and Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, Greece.
Second Department of Dermatology and Venereology, National and Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, Greece.
Dermatol Pract Concept. 2019 Jan 31;9(1):54-62. doi: 10.5826/dpc.0901a13. eCollection 2019 Jan.
mutations are a common finding in malignant melanoma (MM). Nevertheless, apart from their significance as a therapeutic target in advanced melanoma, their prognostic value is still debated.
To assess mutation status in primary, recurrent, or metastatic MM and its correlations with histopathological findings.
We analyzed 203 samples from 178 consecutive patients: 129 primary cutaneous MM, 49 metastatic and recurrent MM of unknown primary site, and 25 cases of recurrences or metastases of primary MM. mutations in exon 15 were identified with real-time polymerase chain reaction and/or direct sequencing or pyrosequencing. Histopathological examination was performed according to standard procedures.
We observed a 42.1% prevalence of mutations at codon 600 among our patients, 84% of whom harbored the V600E mutation. Mutations showed a statistically significant increase in younger patients (P = 0.011), in ulcerated tumors (P = 0.020), and in tumors lacking solar elastosis in adjacent dermis (P = 0.008). Mutations were also more common in male patients, as well as in primary MMs of the torso, and in nonvisceral metastases, however without reaching statistical significance. Logistic regression analysis identified type and ulceration as the only significant predictors of mutation. The highest frequencies of mutated were identified in superficial spreading and nodular types, and the lowest in acral lentiginous and lentigo maligna types. In situ MM and primary dermal melanoma displayed intermediate frequencies.
Frequency of mutated is type-related and correlated with ulceration, a known adverse prognostic factor.
突变在恶性黑色素瘤（MM）中很常见。然而，除了其作为晚期黑色素瘤治疗靶点的意义外，其预后价值仍存在争议。
评估原发性、复发性或转移性MM中的突变状态及其与组织病理学结果的相关性。
我们分析了178例连续患者的203份样本：129例原发性皮肤MM，49例原发部位不明的转移性和复发性MM，以及25例原发性MM的复发或转移病例。通过实时聚合酶链反应和/或直接测序或焦磷酸测序鉴定第15外显子中的突变。根据标准程序进行组织病理学检查。
我们观察到患者中密码子600处的突变发生率为42.1%，其中84%携带V600E突变。突变在年轻患者（P = 0.011）、溃疡肿瘤（P = 0.020）以及相邻真皮中缺乏日光性弹力组织变性的肿瘤（P = 0.008）中在统计学上显著增加。突变在男性患者、躯干原发性MM以及非内脏转移中也更常见，然而未达到统计学显著性。逻辑回归分析确定类型和溃疡是突变的唯一显著预测因素。突变的最高频率在浅表扩散型和结节型中发现，最低频率在肢端雀斑样痣型和恶性雀斑样痣型中发现。原位MM和原发性真皮黑色素瘤显示出中等频率。
突变频率与类型相关，并与溃疡相关，溃疡是一个已知的不良预后因素。
