Marques A R, Espadinha C, Frias M J, Roque L, Catarino A L, Sobrinho L G, Leite V
Centro de Investigação de Patobiologia Molecular, Instituto Português de Oncologia Francisco Gentil, Rua Professor Lima Basto, 1099-023 Lisboa Codex, Portugal.
Br J Cancer. 2004 Aug 16;91(4):732-8. doi: 10.1038/sj.bjc.6601989.
The expression of peroxisome proliferator-activated receptor (PPAR)gamma in thyroid neoplasias and in normal thyroid (NT) tissues has not been fully investigated. The objectives of the present work were: to study and compare the relative expression of PPARgamma in normal, benign and malignant thyroid tissues and to correlate PPARgamma immunostaining with clinical/pathological features of patients with thyroid cancer. We analysed the expression of PPARgamma in several types of thyroid tissues by reverse transcription-polymerase chain reaction (RT-PCR), interphase fluorescent in situ hybridisation, real-time RT-PCR and immunohistochemistry. We have demonstrated that NT tissues express PPARgamma both at mRNA and at protein level. PAX8-PPARgamma fusion gene expression was found in 25% (six of 24) of follicular thyroid carcinomas (FTCs) and in 17% (six of 36) of follicular thyroid adenomas, but in none of the 10 normal tissues, 28 nodular hyperplasias, 38 papillary thyroid carcinomas (PTCs) and 11 poorly differentiated thyroid carcinomas (PDTCs). By real-time RT-PCR, we observed that tumours negative for the PAX8-PPARgamma rearrangement expressed lower levels of PPARgamma mRNA than the NT. Overexpression of PPARgamma transcripts was detected in 80% (four of five) of translocation-positive tumours. Diffuse nuclear staining was significantly (P<0.05) less prevalent in FTCs (53%; 18 of 34), PTCs (49%; 19 of 39) and PDTCs (0%; zero of 13) than in normal tissue (77%; 36 of 47). Peroxisome proliferator-activated receptorgamma-negative FTCs were more likely to be locally invasive, to persist after surgery, to metastasise and to have poorly differentiated areas. Papillary thyroid carcinomas with a predominantly follicular pattern were more often PPARgamma negative than classic PTCs (80% vs 28%; P=0.01). Our results demonstrated that PPARgamma is underexpressed in translocation-negative thyroid tumours of follicular origin and that a further reduction of PPARgamma expression is associated with dedifferentiation at later stages of tumour development and progression.
过氧化物酶体增殖物激活受体（PPAR）γ在甲状腺肿瘤及正常甲状腺（NT）组织中的表达尚未得到充分研究。本研究的目的是：研究并比较PPARγ在正常、良性及恶性甲状腺组织中的相对表达，并将PPARγ免疫染色与甲状腺癌患者的临床/病理特征相关联。我们通过逆转录聚合酶链反应（RT-PCR）、间期荧光原位杂交、实时RT-PCR及免疫组织化学分析了几种类型甲状腺组织中PPARγ的表达情况。我们已证实NT组织在mRNA和蛋白质水平均表达PPARγ。在25%（24例中的6例）的滤泡状甲状腺癌（FTC）和17%（36例中的6例）的滤泡状甲状腺腺瘤中发现了PAX8-PPARγ融合基因表达，但在10例正常组织、28例结节性增生、38例乳头状甲状腺癌（PTC）和11例低分化甲状腺癌（PDTC）中均未发现。通过实时RT-PCR我们观察到，PAX8-PPARγ重排阴性的肿瘤表达的PPARγ mRNA水平低于NT组织。在80%（5例中的4例）的易位阳性肿瘤中检测到PPARγ转录本的过表达。与正常组织（77%；47例中的36例）相比，FTC（53%；34例中的18例）、PTC（49%；39例中的19例）和PDTC（0%；13例中的0例）中的弥漫性核染色明显较少（P<0.05）。PPARγ阴性的FTC更有可能局部浸润、术后持续存在、发生转移并有低分化区域。以滤泡状为主型乳头状甲状腺癌比经典PTC更常呈PPARγ阴性（80%对28%；P=0.01）。我们的结果表明，PPARγ在滤泡起源的易位阴性甲状腺肿瘤中表达不足，并且在肿瘤发展和进展的后期，PPARγ表达的进一步降低与去分化相关。
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