Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York 10065, USA.
Cancer. 2009 Dec 1;115(23):5421-31. doi: 10.1002/cncr.24616.
A subset of follicular lesions of the thyroid is encapsulated similar to follicular adenomas but with partial nuclear features suggestive of papillary thyroid carcinoma (PTC), raising the possibility of biologically borderline tumors.
Gene expression profiling and advanced significance analyses were performed on 50 histologically unequivocal benign and malignant tumors, and a list of 61 differentially expressed genes was generated. By using this 61-gene list, unsupervised hierarchical and K-means cluster analyses were performed on 40 additional tumors, including 15 histologically borderline tumors, 11 benign tumors, and 14 PTCs.
Analysis revealed 3 distinct tumor groups-benign, malignant, and intermediate. Tumors in the intermediate group (n = 15) were mostly histologic borderline tumors and had an expression profile overlapping with the benign and malignant groups. Twenty-seven genes were expressed differentially between the benign and intermediate groups, including the cyclic AMP response element-binding protein/p300-interactivator with glutamic acid/aspartic acid-rich carboxy-terminal domain 1 or CITED1 gene and the fibroblast growth factor receptor 2 or FGFR2 gene. Fourteen genes were expressed differentially between the intermediate group and malignant tumors, notably overexpression of the met proto-oncogene and of the high-mobility group adenine/thymine-hook 2 or HMGA2 gene in malignancies. Mutations of the v-raf murine sarcoma viral oncogene homolog B1 or BRAF gene were identified in 4 of 14 malignant tumors but not in benign or intermediate tumors. Patients who had either histologically or molecularly borderline tumors did not have metastasis or recurrences.
Gene expression profiling supported the finding that encapsulated thyroid follicular lesions with partial nuclear features of PTC are biologically borderline tumors that are distinct molecularly from benign and malignant tumors.
甲状腺滤泡性病变的一个亚组被包裹，类似于滤泡性腺瘤，但具有部分核特征提示甲状腺乳头状癌（PTC），这增加了这些肿瘤具有生物学交界性的可能性。
对 50 例组织学明确的良性和恶性肿瘤进行基因表达谱分析和高级意义分析，并生成了一份 61 个差异表达基因的列表。通过使用这个 61 个基因列表，对另外 40 个肿瘤（包括 15 例组织学交界性肿瘤、11 例良性肿瘤和 14 例 PTC）进行无监督层次聚类和 K-均值聚类分析。
分析显示有 3 个不同的肿瘤组-良性、恶性和中间型。中间型肿瘤（n=15）大多数为组织学交界性肿瘤，其表达谱与良性和恶性肿瘤重叠。良性和中间型肿瘤之间有 27 个基因表达差异，包括环腺苷酸反应元件结合蛋白/ p300-相互作用因子与谷氨酸/天冬氨酸丰富的羧基末端域 1 或 CITED1 基因和成纤维细胞生长因子受体 2 或 FGFR2 基因。中间型和恶性肿瘤之间有 14 个基因表达差异，特别是恶性肿瘤中 MET 原癌基因和高迁移率族蛋白 A2 或 HMGA2 基因的过表达。在 14 例恶性肿瘤中有 4 例检测到 v-raf 鼠肉瘤病毒癌基因同源物 B1 或 BRAF 基因突变，但在良性或中间型肿瘤中没有。组织学或分子学交界性肿瘤的患者没有发生转移或复发。
基因表达谱分析支持这样的发现，即具有部分 PTC 核特征的包裹性甲状腺滤泡性病变是生物学交界性肿瘤，在分子上与良性和恶性肿瘤明显不同。
