Soares Paula, Trovisco Vítor, Rocha Ana Sofia, Feijão Tália, Rebocho Ana Paula, Fonseca Elsa, Vieira de Castro Inês, Cameselle-Teijeiro José, Cardoso-Oliveira Manuel, Sobrinho-Simões Manuel
IPATIMUP (Institute of Molecular Pathology and Immunology of the University of Porto), R. Roberto Frias s/n, 4200 Porto, Portugal.
Virchows Arch. 2004 Jun;444(6):572-6. doi: 10.1007/s00428-004-1018-0. Epub 2004 Apr 17.
Somatic mutations of the BRAF gene (BRAFV599E and BRAFK600E) were found to be closely associated with different histotypes of papillary thyroid carcinoma (PTC). The V599E mutation is highly prevalent in PTC with a papillary or mixed papillary follicular growth pattern, and the K600E mutation is apparently restricted to the follicular variant of PTC. It is usually accepted that thyroid malignancies may follow a progression path from well-differentiated to poorly differentiated (PDC) and undifferentiated (UC) carcinomas. One would expect that at least some of the less differentiated carcinomas would harbour the genetic alterations of pre-existing well-differentiated tumours. In order to find the prevalence of BRAF mutations in PDC and UC, we screened a series of 19 PDCs and 17 UCs, as well as 3 UC-derived cell lines, for both mutation types. The group of PDCs was restricted to the so-called insular and insular-like PDCs, thus excluding PTCs with solid, insular or trabecular foci of growth and PDCs displaying typical PTC nuclei. No BRAF mutations were detected in any of the 19 cases of PDC, whereas 6 of the UCs (35%) and one UC-derived cell line presented the BRAFV599E mutation. The BRAFK600E mutation was not detected in any case. We conclude that UC may progress from BRAFV599E-mutated PTC. The absence of BRAF mutations in our series of PDC supports the assumption that pure insular and insular-like PDCs are more closely related to follicular carcinoma than to PTC.
BRAF基因的体细胞突变（BRAFV599E和BRAFK600E）被发现与甲状腺乳头状癌（PTC）的不同组织学类型密切相关。V599E突变在具有乳头状或乳头状滤泡混合生长模式的PTC中高度普遍，而K600E突变显然仅限于PTC的滤泡变体。通常认为甲状腺恶性肿瘤可能遵循从高分化到低分化（PDC）和未分化（UC）癌的进展路径。人们预期至少一些低分化癌会携带先前存在的高分化肿瘤的基因改变。为了确定BRAF突变在PDC和UC中的发生率，我们对一系列19例PDC、17例UC以及3株UC来源的细胞系进行了两种突变类型的筛查。PDC组仅限于所谓的岛状和岛状样PDC，因此排除了具有实性、岛状或小梁状生长灶的PTC以及显示典型PTC核的PDC。在19例PDC中均未检测到BRAF突变，而6例UC（35%）和1株UC来源的细胞系出现了BRAFV599E突变。在任何病例中均未检测到BRAFK600E突变。我们得出结论，UC可能由BRAFV599E突变的PTC进展而来。我们系列PDC中未检测到BRAF突变支持了这样的假设，即纯岛状和岛状样PDC与滤泡癌的关系比与PTC更密切。
