French Christopher A, Fletcher Jonathan A, Cibas Edmund S, Caulfield Christopher, Allard Paulette, Kroll Todd G
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Endocr Pathol. 2008 Fall;19(3):166-74. doi: 10.1007/s12022-008-9036-0.
The pathologic diagnosis of thyroid follicular tumors is difficult, particularly in preoperative fine-needle aspiration biopsies. To investigate whether the molecular diagnosis of PPAR gamma rearrangements can detect thyroid carcinomas in fine-needle aspiration biopsies, we performed interphase fluorescence in situ hybridization on 24 thyroid fine-needle aspiration and 17 follow-up thyroidectomy specimens. Two of the 24 fine-needle aspiration biopsies contained PPAR gamma rearrangements, and both were diagnosed suggestive of a thyroid follicular neoplasm by cytology. The two corresponding thyroidectomies each contained PPAR gamma rearrangements in all tumor cells and, both were diagnosed follicular-patterned thyroid carcinomas-one a follicular carcinoma and the other a follicular variant of papillary carcinoma, the latter by majority of expert endocrine pathologists. Our experiments demonstrate that PPAR gamma rearrangements can detect a subset of follicular-patterned thyroid carcinomas in preoperative thyroid fine-needle aspiration biopsies. The ultimate utility of mutations such as PPAR gamma rearrangements in diagnosis of thyroid carcinoma must be proven by direct correlation of mutation status with thyroid tumor biology and not just with thyroid tumor morphology, a subjective and imprecise marker of clinical behavior. The application of specific mutations to preoperative diagnosis of thyroid carcinoma is predicted to improve the accuracy and reduce the costs of treating patients with thyroid tumors.
甲状腺滤泡性肿瘤的病理诊断较为困难，尤其是在术前细针穿刺活检中。为了研究PPARγ重排的分子诊断能否在细针穿刺活检中检测出甲状腺癌，我们对24份甲状腺细针穿刺样本和17份后续甲状腺切除术标本进行了间期荧光原位杂交。24份细针穿刺活检中有两份含有PPARγ重排，细胞学诊断均提示为甲状腺滤泡性肿瘤。相应的两份甲状腺切除术标本中，所有肿瘤细胞均含有PPARγ重排，且均被诊断为滤泡型甲状腺癌——一份为滤泡癌，另一份为乳头状癌的滤泡变异型，后者由大多数内分泌病理专家确诊。我们的实验表明，PPARγ重排在术前甲状腺细针穿刺活检中能够检测出一部分滤泡型甲状腺癌。诸如PPARγ重排等突变在甲状腺癌诊断中的最终效用必须通过突变状态与甲状腺肿瘤生物学的直接关联来证明，而不仅仅是与甲状腺肿瘤形态相关，因为形态是临床行为的主观且不准确的指标。预计将特定突变应用于甲状腺癌的术前诊断可提高准确性并降低甲状腺肿瘤患者的治疗成本。
