Department of Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Japan.
Histopathology. 2010 Sep;57(3):444-50. doi: 10.1111/j.1365-2559.2010.03646.x.
To elucidate the genetic background of anaplastic transformation, RET rearrangements and BRAF mutation were studied in composite undifferentiated carcinomas (UCs) of the thyroid, which are UCs having papillary carcinoma (PC) components.
Reverse transcription-polymerase chain reaction (RT-PCR) was performed for RET rearrangements and PCR for BRAF mutation in UC and PC components that were microdissected separately from seven composite UCs. Forty-two thyroid cancers with single component histology (14 UCs and 28 PCs) were also studied in the same manner. RET/PTC1 was undetectable in both components from all seven composite UCs, and RET/PTC3 was identified in both components of one composite UC. BRAF mutation was identified in both components from three composite UCs and only in the PC components from two composite UCs. In contrast, in thyroid carcinomas with single component histology, RET/PTC1 was detected in 11% of PCs and in none of the UCs, and RET/PTC3 was not found in any of the tumours studied. BRAF mutation was identified in 82% of PCs and in 21% of UCs.
The high frequency of BRAF mutation and the absence of RET rearrangements in UC components from composite UCs supports the hypothesis that UCs may actually represent progressive malignant degeneration of a BRAF-mutated, well-differentiated thyroid carcinoma.
阐明间变性转化的遗传背景，研究了甲状腺复合未分化癌（UC）中 RET 重排和 BRAF 突变，这些癌是具有乳头状癌（PC）成分的 UC。
从 7 例复合 UC 中分别微切割 UC 和 PC 成分，对其进行逆转录-聚合酶链反应（RT-PCR）检测 RET 重排和 PCR 检测 BRAF 突变。还以同样的方式研究了 42 例具有单一成分组织学的甲状腺癌（14 例 UC 和 28 例 PC）。在所有 7 例复合 UC 的两个成分中均未检测到 RET/PTC1，在 1 例复合 UC 的两个成分中均检测到 RET/PTC3。在 3 例复合 UC 的两个成分中均鉴定出 BRAF 突变，在 2 例复合 UC 的两个成分中仅鉴定出 BRAF 突变。相比之下，在具有单一成分组织学的甲状腺癌中，11%的 PC 中检测到 RET/PTC1，而在 UC 中则未检测到，在研究的所有肿瘤中均未发现 RET/PTC3。BRAF 突变在 82%的 PC 和 21%的 UC 中被鉴定出来。
复合 UC 的 UC 成分中 BRAF 突变的高频和 RET 重排的缺失支持了这样的假设，即 UC 实际上可能代表 BRAF 突变的、分化良好的甲状腺癌恶性进展的结果。
