Kakavand Hojabr, Crainic Oana, Lum Trina, O'Toole Sandra A, Kefford Richard F, Thompson John F, Wilmott James S, Long Georgina V, Scolyer Richard A
1The University of Sydney, Sydney 2Melanoma Institute Australia, North Sydney 3Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia 4Canterbury Health Laboratories, Christchurch, New Zealand 5Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst 6Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Pathology. 2014 Apr;46(3):193-8. doi: 10.1097/PAT.0000000000000077.
There is concern that BRAF mutant naevus cells admixed with melanoma cells could cause false positive mutation tests in BRAF wild-type melanomas. We sought to assess the frequency of BRAF(V600E) mutations in primary melanomas arising with/without associated naevi and determine BRAF(V600E) concordance between melanomas and associated naevi. Formalin fixed, paraffin embedded (FFPE) tissue from 57 patients with primary melanomas with/without associated naevi was immunohistochemically stained to detect BRAF(V600E) mutation. In a subset of patients (n = 29), molecular mutation testing was also carried out using a panel of 238 known genetic variants. Of the primary melanomas with an associated naevus (n = 29), 55% were BRAF(V600E) mutant with 100% concordance between the melanoma and associated naevus. In contrast, only 21% of the primary melanomas unassociated with naevi were BRAF(V600E) mutant (p = 0.009).Our results suggest that melanomas with associated naevi have a higher frequency of BRAF(V600E) mutations than melanomas unassociated with naevi. Furthermore, melanomas and their associated naevi were concordant in BRAF(V600E) status, which suggests that false positive mutation tests occurring as a consequence of admixed BRAF mutant naevus cells in BRAF wild-type primary melanomas are unlikely to be a problem in clinical practice. The findings have important implications for adjuvant clinical trials of targeted therapies.
有人担心，与黑色素瘤细胞混合的BRAF突变痣细胞可能会在BRAF野生型黑色素瘤中导致假阳性突变检测结果。我们试图评估伴有/不伴有相关痣的原发性黑色素瘤中BRAF（V600E）突变的频率，并确定黑色素瘤与其相关痣之间BRAF（V600E）的一致性。对57例伴有/不伴有相关痣的原发性黑色素瘤患者的福尔马林固定、石蜡包埋（FFPE）组织进行免疫组织化学染色，以检测BRAF（V600E）突变。在一部分患者（n = 29）中，还使用一组238个已知基因变异进行了分子突变检测。在伴有相关痣的原发性黑色素瘤（n = 29）中，55%为BRAF（V600E）突变型，黑色素瘤与其相关痣之间的一致性为100%。相比之下，与痣无关的原发性黑色素瘤中只有21%为BRAF（V600E）突变型（p = 0.009）。我们的结果表明，伴有相关痣的黑色素瘤比与痣无关的黑色素瘤具有更高频率的BRAF（V600E）突变。此外，黑色素瘤及其相关痣在BRAF（V600E）状态上是一致的，这表明在BRAF野生型原发性黑色素瘤中，由于BRAF突变痣细胞混合而导致的假阳性突变检测结果在临床实践中不太可能成为问题。这些发现对靶向治疗的辅助临床试验具有重要意义。
