Genetic and biological subgroups of low-stage follicular thyroid cancer
Genetic and biological subgroups of low-stage follicular thyroid cancer
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DOI：
10.1016/s0002-9440(10)63902-8
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发表时间：
2003-04-01
影响因子：
6
通讯作者：
Kroll, TG
中科院分区：
文献类型：
--
作者：
French, CA;Alexander, EK;Kroll, TG
癌症特异性基因重排的研究增加了我们对人类肿瘤的理解，并导致在血细胞和结缔组织恶性肿瘤的病理诊断中使用重排。在这里，我们研究了人类甲状腺滤泡上皮肿瘤中过氧化物酶体增殖物激活受体γ (PPAR γ)基因的3p25重排。42例低期滤泡癌中有11例（26%），40例滤泡腺瘤中有0例，30例Hurthle细胞癌中有1例，90例乳头状癌中有1例，10例结节性甲状腺肿中有0例经间期荧光原位杂交发现3p25重排。所有11例3p25重排的滤泡癌均表现出对PPARgamma强烈的弥漫性核免疫反应性，与PPARgamma融合蛋白的表达一致。42例（29%）低期滤泡癌中有12例（3p25）无PPARgamma重排（P = 0.01），提示PPARgamma重排和非整倍体是独立的滤泡癌早期事件。12例3p25腺瘤的滤泡癌中有11例未表现出PPARgamma免疫反应性，支持两种独立通路的存在。与无PPARgamma重排的滤泡癌患者相比，有PPARgamma重排的滤泡癌患者有更多的血管侵犯（P = 0.01）、实性/巢状肿瘤组织学面积（P < 0.001）和既往非甲状腺癌（P < 0.01）。我们的实验确定了低阶段滤泡性甲状腺癌的遗传亚群，并提供证据表明滤泡性甲状腺癌具有PPARgamma重排是一个独特的生物学实体。这些发现支持了一个模型，即在甲状腺癌亚型中，不同的遗传改变启动了不同的肿瘤发生途径。
Investigations of cancer-specific gene rearrangements have increased our understanding of human neoplasia and led to the use of the rearrangements in pathological diagnosis of blood cell and connective tissue malignancies. Here, we have investigated 3p25 rearrangements of the peroxisome proliferator-activated receptor gamma (PPAR gamma) gene in follicular epithelial tumors of the human thyroid gland. Eleven of 42 (26%) low-stage follicular carcinomas, 0 of 40 follicular adenomas, 1 of 30 Hurthle cell carcinomas, 1 of 90 papillary carcinomas, and 0 of 10 nodular goiters had 3p25 rearrangements by interphase fluorescence in situ hybridization. All 11 follicular carcinomas with 3p25 rearrangement exhibited strong, diffuse nuclear immunoreactivity for PPARgamma, consistent with expression of PPARgamma fusion protein. Twelve of 42 (29%) low-stage follicular carcinomas had 3p25 aneusomy without PPARgamma rearrangement (P = 0.01), suggesting that PPARgamma rearrangement and aneuploidy are independent early events in follicular cancer. Eleven of 12 follicular carcinomas with 3p25 aneusomy exhibited no PPARgamma immunoreactivity, supporting the existence of two independent pathways. Follicular carcinoma patients with PPARgamma rearrangement more frequently had vascular invasion (P = 0.01), areas of solid/nested tumor histology (P < 0.001), and previous nonthyroid cancers (P < 0.01) compared with follicular carcinoma patients without PPARgamma rearrangement. Our experiments identify genetic subgroups of low-stage follicular thyroid cancer and provide evidence that follicular carcinomas with PPARgamma rearrangement are a distinct biological entity. The findings support a model in which separate genetic alterations initiate distinct pathways of oncogenesis in thyroid carcinoma subtypes.