Chen Yao-Tseng, Kitabayashi Naoki, Zhou Xi K, Fahey Thomas J, Scognamiglio Theresa
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Mod Pathol. 2008 Sep;21(9):1139-46. doi: 10.1038/modpathol.2008.105. Epub 2008 Jun 27.
MicroRNA (miRNA) microarray analysis has consistently found altered expression of miRNAs in thyroid tumors, suggesting their roles in thyroid carcinogenesis. To explore whether this differential expression can be used as a diagnostic tool in surgical pathology and fine-needle aspirate (FNA) specimens, the expression of selected miRNA was evaluated by quantitative RT-PCR, using total RNA from 84 formalin-fixed paraffin-embedded tissues and 40 ex vivo aspirate specimens. miRNA from all paraffin-embedded tissues and all but one FNA sample were found to be analyzable, with paraffin sections yielding better miRNA quality. Preliminary analysis of 6 miRNAs in 10 papillary thyroid carcinoma and 10 follicular adenoma identified significant overexpression of miR-146b, -221, and -222 in papillary thyroid carcinoma (P<0.02), but not miR-146a, -155, or -187 (P>0.08). The expression of these first three miRNAs was examined in a series of 5 normal thyroid, 11 hyperplastic nodules, 24 follicular adenoma, 27 classical papillary thyroid carcinoma, 5 follicular variant papillary thyroid carcinoma, 2 follicular carcinoma, and 10 encapsulated follicular lesions with partial nuclear features of papillary carcinoma. Results showed miR-146b to be most consistently overexpressed in both classical papillary carcinoma and follicular variants, whereas all other groups showed lower expression at a similar level (P<0.001 for pair-wise comparisons between papillary carcinoma and all other groups). Follicular lesions with partial features of papillary carcinoma all showed low miR-146b levels similar to other non-papillary carcinoma groups, suggesting that they are biologically distinctive from papillary carcinoma. miR-221 and miR-222 also showed higher expression in papillary carcinoma, but with substantial overlaps with the other groups. When applied to 40 FNA samples of various lesions, only miR-146b and miR-222 persisted as distinguishing markers for papillary carcinoma. We concluded that miRNAs, particularly miR-146b, might potentially be adjunct markers for diagnosing papillary thyroid carcinoma in both FNA and surgical pathology specimens.
微小RNA（miRNA）微阵列分析一直发现甲状腺肿瘤中miRNA的表达发生改变，提示它们在甲状腺癌发生过程中发挥作用。为了探究这种差异表达是否可作为手术病理和细针穿刺抽吸（FNA）标本的诊断工具，我们使用来自84个福尔马林固定石蜡包埋组织和40个离体抽吸标本的总RNA，通过定量逆转录聚合酶链反应（RT-PCR）评估了所选miRNA的表达。发现所有石蜡包埋组织以及除一个FNA样本外的所有样本中的miRNA均可分析，石蜡切片产生的miRNA质量更好。对10例乳头状甲状腺癌和10例滤泡性腺瘤中的6种miRNA进行初步分析，发现miR-146b、-221和-222在乳头状甲状腺癌中显著过表达（P<0.02），而miR-146a、-155或-187则不然（P>0.08）。在一系列5例正常甲状腺、11例增生性结节、24例滤泡性腺瘤、27例经典乳头状甲状腺癌、5例滤泡状变异型乳头状甲状腺癌、2例滤泡癌以及10例具有部分乳头状癌核特征的包膜滤泡性病变中检测了这前三种miRNA的表达。结果显示，miR-146b在经典乳头状癌和滤泡状变异型中均最持续地过表达，而所有其他组的表达水平相似且较低（乳头状癌与所有其他组之间的两两比较P<0.001）。具有部分乳头状癌特征的滤泡性病变均显示出与其他非乳头状癌组相似的低miR-146b水平，表明它们在生物学上与乳头状癌不同。miR-221和miR-222在乳头状癌中也显示出较高表达，但与其他组有大量重叠。当应用于40个各种病变的FNA样本时，只有miR-146b和miR-222仍然是乳头状癌的鉴别标志物。我们得出结论，miRNA，尤其是miR-146b，可能潜在地作为FNA和手术病理标本中诊断乳头状甲状腺癌的辅助标志物。
