Maia F F R, Vassallo J, Pinto G A, Pavin E J, Matos P S, Zantut-Wittmann D E
Endocrinology Division, Department of Internal Medicine, University of Campinas, São Paulo, Brazil.
Department of Pathology, Medical Science School, University of Campinas, São Paulo, Brazil.
Exp Clin Endocrinol Diabetes. 2016 Apr;124(4):209-14. doi: 10.1055/s-0035-1569363. Epub 2016 Apr 28.
Studying molecules that are differentially expressed in cancers as well as benign and normal tissues is crucial for identifying novel biomarkers for cancer immunotherapy. This study aimed to investigate the clinical utility of the immunochemical expression of the proliferative cell marker Ki-67 and the apoptotic blocker Mcl-1 in papillary thyroid carcinoma (PTC).
We built a tissue microarray with 282 thyroid specimens. There were 59 PTCs including 35 classic (CPTC), 3 tall cell (TCPTC) and 21 follicular variants (FVPTC); 79 benign thyroid diseases (22 follicular adenomas; 57 adenomatoid hyperplasia); 33 Hashimoto's thyroiditis (HT) specimens; and 111 normal thyroid tissues. Clinical history and ultrasound data were retrospectively obtained by chart review.
Mcl-1 overexpression was evident in 66.7% of the PTC tissues compared to 32% of the benign thyroid diseases. Mcl-1 strong staining distinguished benign from malignant thyroid lesions (sensitivity=61.3%; specificity=72.8%; negative predictive value, NPV=68%; positive predictive value, PPV=66.7% and 67.5% accuracy). Positive nuclear Ki-67 staining was observed in 34% of PTCs vs. 19% of thyroid adenomas (P=0.031). Strong Mcl-1 and Ki-67 co-expression was identified in 57.5% of PTCs with a higher PPV (75.8%). Mcl-1 and Ki-67 expression was not associated with any clinicopathological feature of malignancy. No deaths occurred during the follow-up.
Mcl-1 immunochemical overexpression allowed differentiating low-risk PTC from the benign thyroid lesions. We suggest that Mcl-1 expression may help differentiate follicular patterned thyroid lesions. The influence of the Mcl-1 expression on several features of tumor aggressiveness has to be studied in large series of high-risk thyroid carcinomas.
研究在癌症以及良性和正常组织中差异表达的分子对于识别癌症免疫治疗的新型生物标志物至关重要。本研究旨在探讨增殖细胞标志物Ki-67和凋亡阻断剂Mcl-1的免疫化学表达在甲状腺乳头状癌（PTC）中的临床应用价值。
我们构建了一个包含282个甲状腺标本的组织微阵列。其中有59例PTC，包括35例经典型（CPTC）、3例高细胞型（TCPTC）和21例滤泡变异型（FVPTC）；79例良性甲状腺疾病（22例滤泡性腺瘤；57例腺瘤样增生）；33例桥本甲状腺炎（HT）标本；以及111例正常甲状腺组织。通过查阅病历回顾性获取临床病史和超声数据。
与32%的良性甲状腺疾病相比，66.7%的PTC组织中Mcl-1过表达明显。Mcl-1强染色可区分甲状腺良性与恶性病变（敏感性=61.3%；特异性=72.8%；阴性预测值，NPV=68%；阳性预测值，PPV=66.7%，准确性=67.5%）。34%的PTC中观察到核Ki-67阳性染色，而甲状腺腺瘤中为19%（P=0.031）。57.5%的PTC中鉴定出Mcl-1和Ki-67强共表达，PPV更高（75.8%）。Mcl-1和Ki-67表达与任何恶性肿瘤的临床病理特征均无关联。随访期间无死亡病例。
Mcl-1免疫化学过表达有助于将低风险PTC与良性甲状腺病变区分开来。我们认为Mcl-1表达可能有助于鉴别滤泡型甲状腺病变。Mcl-1表达对大量高危甲状腺癌肿瘤侵袭性的若干特征的影响有待进一步研究。
