Abstract：
BACKGROUND: The clinicopathologic and genetic features of cutaneous melanoma with a BRAF V600K mutation are not well-known. We aimed to evaluate these characteristics in comparison with those associated with BRAF V600E.
METHODS: Real-time polymerase chain reaction (PCR) and/or the MassARRAY® system were used to detect BRAF V600K in 16 invasive melanomas and confirm BRAF V600E in another 60 cases. Immunohistochemistry and panel next-generation sequencing were used to evaluate protein expression and tumor mutation burden, respectively.
RESULTS: The median age of melanoma patients harboring the BRAF V600K mutation (72.5 years) was higher than those with the BRAF V600E (58.5 years). The two groups also differed in sex (13/16 [81.3%] male in the V600K group vs. 23/60 [38.3%] in V600E) and in the frequency of scalp involvement (8/16 [50.0%] in V600K vs. 1/60 [1.6%] in V600E). The clinical appearance was similar to a superficial spreading melanoma. Histopathologically, non-nested lentiginous intraepidermal spread and subtle solar elastosis were observed. One patient (1/13, 7.7%) had a pre-existing intradermal nevus. Diffuse PRAME immunoexpression was seen in only one (14.3%) of seven tested cases. Loss of p16 expression was observed in all 12 cases (100%) analyzed. The tumor mutation burden was 8 and 6 mutations/Mb in the two tested cases.
CONCLUSIONS: Melanoma carrying the BRAF V600K mutation showed the predominance on the scalp of elderly men, lentiginous intraepidermal growth, subtle solar elastosis, possible existence of intradermal nevus component, frequent loss of p16 immunoexpression, limited immunoreactivity for PRAME, and intermediate tumor mutation burden.
METHODS: Real-time polymerase chain reaction (PCR) and/or the MassARRAY® system were used to detect BRAF V600K in 16 invasive melanomas and confirm BRAF V600E in another 60 cases. Immunohistochemistry and panel next-generation sequencing were used to evaluate protein expression and tumor mutation burden, respectively.
RESULTS: The median age of melanoma patients harboring the BRAF V600K mutation (72.5 years) was higher than those with the BRAF V600E (58.5 years). The two groups also differed in sex (13/16 [81.3%] male in the V600K group vs. 23/60 [38.3%] in V600E) and in the frequency of scalp involvement (8/16 [50.0%] in V600K vs. 1/60 [1.6%] in V600E). The clinical appearance was similar to a superficial spreading melanoma. Histopathologically, non-nested lentiginous intraepidermal spread and subtle solar elastosis were observed. One patient (1/13, 7.7%) had a pre-existing intradermal nevus. Diffuse PRAME immunoexpression was seen in only one (14.3%) of seven tested cases. Loss of p16 expression was observed in all 12 cases (100%) analyzed. The tumor mutation burden was 8 and 6 mutations/Mb in the two tested cases.
CONCLUSIONS: Melanoma carrying the BRAF V600K mutation showed the predominance on the scalp of elderly men, lentiginous intraepidermal growth, subtle solar elastosis, possible existence of intradermal nevus component, frequent loss of p16 immunoexpression, limited immunoreactivity for PRAME, and intermediate tumor mutation burden.
摘要：
背景：具有BRAFV600K突变的皮肤黑色素瘤的临床病理和遗传特征尚不为人所知。我们的目的是将这些特征与与BRAFV600E相关的特征进行比较。
方法：使用实时聚合酶链反应（PCR）和/或MassARRAY®系统检测16例侵袭性黑素瘤中的BRAFV600K，并在另外60例中确认BRAFV600E。免疫组织化学和小组下一代测序用于评估蛋白质表达和肿瘤突变负荷，分别。
结果：携带BRAFV600K突变的黑色素瘤患者的中位年龄（72.5岁）高于BRAFV600E患者（58.5岁）。两组的性别也有所不同（V600K组中13/16[81.3％]男性与V600E中的23/60[38.3％]）和头皮受累频率（V600K中的8/16[50.0％]与V600E中的1/60[1.6%]）。临床表现类似于浅表扩散的黑色素瘤。组织病理学,观察到非嵌套的浅色表皮内扩散和细微的日光弹性增生。一名患者（1/13，7.7％）患有预先存在的皮内痣。在7例测试病例中仅有1例（14.3％）出现弥漫性PRAME免疫表达。在所有12例(100%)分析中观察到p16表达的缺失。在两个测试病例中,肿瘤突变负荷为8和6个突变/Mb。
结论：携带BRAFV600K突变的黑色素瘤在老年男性头皮上占优势，浅色表皮内生长，微妙的日光弹性沉着症，可能存在皮内痣成分，p16免疫表达频繁丧失，PRAME的有限免疫反应性，和中等肿瘤突变负担。
方法：使用实时聚合酶链反应（PCR）和/或MassARRAY®系统检测16例侵袭性黑素瘤中的BRAFV600K，并在另外60例中确认BRAFV600E。免疫组织化学和小组下一代测序用于评估蛋白质表达和肿瘤突变负荷，分别。
结果：携带BRAFV600K突变的黑色素瘤患者的中位年龄（72.5岁）高于BRAFV600E患者（58.5岁）。两组的性别也有所不同（V600K组中13/16[81.3％]男性与V600E中的23/60[38.3％]）和头皮受累频率（V600K中的8/16[50.0％]与V600E中的1/60[1.6%]）。临床表现类似于浅表扩散的黑色素瘤。组织病理学,观察到非嵌套的浅色表皮内扩散和细微的日光弹性增生。一名患者（1/13，7.7％）患有预先存在的皮内痣。在7例测试病例中仅有1例（14.3％）出现弥漫性PRAME免疫表达。在所有12例(100%)分析中观察到p16表达的缺失。在两个测试病例中,肿瘤突变负荷为8和6个突变/Mb。
结论：携带BRAFV600K突变的黑色素瘤在老年男性头皮上占优势，浅色表皮内生长，微妙的日光弹性沉着症，可能存在皮内痣成分，p16免疫表达频繁丧失，PRAME的有限免疫反应性，和中等肿瘤突变负担。
