Trovisco Vítor, Vieira de Castro Inês, Soares Paula, Máximo Valdemar, Silva Paula, Magalhães João, Abrosimov Alexander, Guiu Xavier Matias, Sobrinho-Simões Manuel
IPATIMUP (Institute of Molecular Pathology and Immunology of the University of Porto), Porto, Portugal.
J Pathol. 2004 Feb;202(2):247-51. doi: 10.1002/path.1511.
Mutations in the BRAF gene have recently been detected in a wide range of neoplastic lesions with a particularly high prevalence in melanoma and papillary thyroid carcinoma (PTC). The hot-spot mutation BRAF(V599E) is frequently detected in PTC (36-69%), in contrast to its absence in other benign or malignant thyroid lesions. In order to unravel whether there is any association between the occurrence of the BRAF mutation and the histological pattern of PTC, in this study a previous series of 50 PTCs was extended to 134 cases, including ten cases of PTC-related entities-hyalinizing trabecular tumour (HTT) and mucoepidermoid carcinoma (MEC). Using PCR/SSCP and sequencing, the BRAF(V599E) mutation was detected in 45 of the 124 PTCs (36%). No mutations were detected in any case of HTT and MEC. BRAF(V599E) was present in 75% of Warthin-like PTCs and 53% of conventional PTCs, whereas no BRAF(V599E) mutations were detected in any of the 32 cases of the follicular variant of PTC. BRAF(V599E) was also detected in 6 of 11 cases of the oncocytic variant of PTC that displayed a papillary or mixed follicular-papillary growth pattern and in none of the four oncocytic PTCs with a follicular growth pattern. A distinct mutation in BRAF (codon K600E) was detected in three cases of the follicular variant of PTC. This study has confirmed the high prevalence of BRAF(V599E) in PTC and has shown that the mutation is almost exclusively seen in PTC with a papillary or mixed follicular-papillary growth pattern, regardless of the cytological features of the neoplastic cells. The results support the existence of an oncocytic variant of PTC that should be separated from the oncocytic variant of follicular carcinoma and suggest that the follicular variant of PTC may be genetically different from conventional PTC.
最近在多种肿瘤性病变中检测到BRAF基因的突变，在黑色素瘤和甲状腺乳头状癌（PTC）中尤为常见。热点突变BRAF(V599E)在PTC中经常被检测到（36%-69%），而在其他良性或恶性甲状腺病变中则未检测到。为了阐明BRAF突变的发生与PTC的组织学模式之间是否存在任何关联，在本研究中，先前的一系列50例PTC扩展至134例，包括10例与PTC相关的实体——透明变梁状肿瘤（HTT）和黏液表皮样癌（MEC）。使用PCR/SSCP和测序方法，在124例PTC中的45例（36%）检测到BRAF(V599E)突变。在任何HTT和MEC病例中均未检测到突变。BRAF(V599E)存在于75%的沃辛样PTC和53%的传统PTC中，而在32例滤泡状PTC变体中均未检测到BRAF(V599E)突变。在11例呈现乳头状或滤泡-乳头状混合生长模式的嗜酸性细胞变体PTC中，有6例检测到BRAF(V599E)，而在4例具有滤泡状生长模式的嗜酸性细胞PTC中均未检测到。在3例滤泡状PTC变体中检测到BRAF的一个独特突变（密码子K600E）。本研究证实了BRAF(V599E)在PTC中的高发生率，并表明该突变几乎仅见于具有乳头状或滤泡-乳头状混合生长模式的PTC，而与肿瘤细胞的细胞学特征无关。结果支持存在一种应与滤泡癌嗜酸性细胞变体相区分的PTC嗜酸性细胞变体，并提示PTC滤泡状变体可能在基因上与传统PTC不同。
