Chiappetta G, Tallini G, De Biasio M C, Manfioletti G, Martinez-Tello F J, Pentimalli F, de Nigris F, Mastro A, Botti G, Fedele M, Berger N, Santoro M, Giancotti V, Fusco A
Istituto Nazionale dei Tumori di Napoli, Fondazione Senatore Pascale, Università di Napoli Federico II, Naples, Italy.
Cancer Res. 1998 Sep 15;58(18):4193-8.
Hyperplastic or neoplastic proliferative lesions of thyroid follicular epithelium consist of a spectrum, ranging from nodular hyperplasia to undifferentiated (anaplastic) carcinoma, and usually present as palpable thyroid nodules. Thyroid nodules are a common occurrence in the general population, but only a small proportion of them are eventually diagnosed as carcinoma. The difficulty in objectively identifying those thyroid nodules that are malignant to avoid unnecessary surgery, combined with the range and effectiveness of the available therapeutic options in those patients who do, indeed, have thyroid carcinoma, has prompted the search for tumor markers and prognostic indicators. The high mobility group I (HMGI) proteins represent a class of nuclear proteins involved in the regulation of chromatin structure and function. HMGI(Y), one of the members of this class, is expressed at high levels during embryogenesis and in malignant tumors but at generally low levels in normal adult human tissues. Previous work on a limited number of thyroid samples suggested that the detection of the HMGI(Y) proteins may provide a clinically useful diagnostic tool. To verify this assumption, we analyzed HMGI(Y) expression by a combination of immunohistochemistry and reverse transcription-PCR in 358 thyroid tissue samples that were representative of the spectrum of thyroid tumor pathology. HMGI(Y) was detectable in 18 of 19 follicular carcinomas, 92 of 96 papillary carcinomas, and 11 of 11 undifferentiated (anaplastic) carcinomas but in only 1 of 20 hyperplastic nodules, 44 of 200 follicular adenomas, and 0 of 12 normal tissue samples. The correlation between HMGI(Y) expression and a diagnosis of carcinoma was highly significant (P < 0.0001). We also prospectively collected and analyzed for HMGI(Y) expression by immunohistochemistry and reverse transcription-PCR in 12 fine needle aspiration biopsies from 10 patients who subsequently underwent surgical removal of a solitary thyroid nodule. HMGI(Y) was detectable only in the four fine needle aspiration biopsies, corresponding to the thyroid nodules that were definitively diagnosed as carcinomas after surgery (two follicular carcinomas and two papillary carcinomas). The remaining eight samples (six follicular adenomas and two samples consisting of normal follicular cells) were negative. The findings of this study confirm the differential expression of HMGI(Y) in thyroid neoplasia and indicate the HMGI(Y) protein as a potential marker for thyroid carcinoma.
甲状腺滤泡上皮的增生性或肿瘤性增殖性病变包括一系列情况，从结节性增生到未分化（间变性）癌，通常表现为可触及的甲状腺结节。甲状腺结节在普通人群中很常见，但最终只有一小部分会被诊断为癌。客观识别那些恶性的甲状腺结节以避免不必要的手术存在困难，再加上对于确实患有甲状腺癌的患者，现有治疗选择的范围和有效性，促使人们寻找肿瘤标志物和预后指标。高迁移率族I（HMGI）蛋白是一类参与染色质结构和功能调节的核蛋白。该类成员之一的HMGI(Y)在胚胎发育过程中和恶性肿瘤中高水平表达，但在正常成人组织中通常低水平表达。先前对有限数量甲状腺样本的研究表明，检测HMGI(Y)蛋白可能提供一种临床有用的诊断工具。为了验证这一假设，我们通过免疫组织化学和逆转录聚合酶链反应相结合的方法，分析了358份代表甲状腺肿瘤病理谱的甲状腺组织样本中的HMGI(Y)表达。在19例滤泡癌中的18例、96例乳头状癌中的92例以及11例未分化（间变性）癌中的11例中可检测到HMGI(Y)，但在20例增生性结节中的1例、200例滤泡性腺瘤中的第44例以及12例正常组织样本中均未检测到。HMGI(Y)表达与癌诊断之间的相关性非常显著（P < 0.0001）。我们还前瞻性地收集并通过免疫组织化学和逆转录聚合酶链反应分析了10例患者的12份细针穿刺活检样本中的HMGI(Y)表达，这些患者随后接受了单个甲状腺结节的手术切除。仅在4份细针穿刺活检样本中可检测到HMGI(Y)，对应于术后被明确诊断为癌的甲状腺结节（2例滤泡癌和2例乳头状癌）。其余8份样本（6例滤泡性腺瘤和2份由正常滤泡细胞组成的样本）为阴性。本研究结果证实了HMGI(Y)在甲状腺肿瘤中的差异表达，并表明HMGI(Y)蛋白是甲状腺癌的潜在标志物。
