Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
Endocrine. 2018 Aug;61(2):293-302. doi: 10.1007/s12020-018-1627-z. Epub 2018 May 23.
Preoperative distinction of follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA) is a diagnostic challenge. Our aim was to investigate whether the Ki-67 proliferation index in fine needle aspiration material can contribute to the diagnosis of FTC.
We analyzed retrospectively cytological Ki-67 index determined in routine clinical setting and clinical data for 61 patients with FTC, 158 patients with FTA and 15 patients with follicular tumor of uncertain malignant potential (FT-UMP) surgically treated and diagnosed by histopathology at Karolinska University Hospital 2006-2017 (Cohort A). A previously published cohort of 109 patients with follicular tumors was re-analyzed as well (Cohort B).
In Cohort A, patients with FTC had a higher Ki-67 index (p < 0.001), larger tumor size (p < 0.001) and higher age at diagnosis (p = 0.036) compared to patients with FTA or FT-UMP. Hürthle cell differentiation, present in 50 FTA, 20 FTC and 8 FT-UMP, was associated with higher Ki-67 index (p = 0.009). Multivariate analysis of Cohort A identified a high Ki-67 index (odds ratio [OR]: 1.215, p < 0.001) and large tumor size (OR: 1.038, p < 0.001) as independent predictors of FTC. Results remained consistent after exclusion of Hürthle cell tumors and in pooled analysis of Cohort A + B. The area under curve of the Ki-67 index for predicting FTC was 0.722 and a cut-off for Ki-67 index at above 5% resulted in a specificity at 93% and sensitivity at 31%. Subgroup analysis of FTCs in Cohort A showed an association of higher Ki-67 index to extrathyroidal extension (p = 0.001) as well as widely invasive subtype (p = 0.019) based on the WHO 2017 classification.
Pre-operative Ki-67 index may add diagnostic information for a subset of patients with follicular thyroid tumors.
术前区分滤泡状甲状腺癌（FTC）和滤泡状甲状腺腺瘤（FTA）具有诊断挑战性。我们的目的是研究细针抽吸物中的 Ki-67 增殖指数是否有助于 FTC 的诊断。
我们回顾性分析了 2006 年至 2017 年在卡罗林斯卡大学医院接受手术治疗并通过组织病理学诊断为 FTC 的 61 例、FTA 的 158 例和滤泡性肿瘤性质不确定（FT-UMP）的 15 例患者的常规临床检测中的细胞学 Ki-67 指数和临床数据（Cohort A）。我们还重新分析了之前发表的 109 例滤泡性肿瘤患者的队列（Cohort B）。
在 Cohort A 中，与 FTA 或 FT-UMP 患者相比，FTC 患者的 Ki-67 指数更高（p<0.001）、肿瘤更大（p<0.001）且诊断时年龄更大（p=0.036）。50 例 FTA、20 例 FTC 和 8 例 FT-UMP 存在 Hurthle 细胞分化，与更高的 Ki-67 指数相关（p=0.009）。Cohort A 的多变量分析确定高 Ki-67 指数（优势比[OR]：1.215，p<0.001）和大肿瘤大小（OR：1.038，p<0.001）是 FTC 的独立预测因素。排除 Hurthle 细胞肿瘤后，结果在 Cohort A+B 的汇总分析中保持一致。Ki-67 指数预测 FTC 的曲线下面积为 0.722，Ki-67 指数大于 5%的截断值可使特异性达到 93%，敏感性为 31%。Cohort A 中 FTC 的亚组分析显示，Ki-67 指数与甲状腺外延伸（p=0.001）以及广泛侵袭性亚型（p=0.019）相关，这是基于 2017 年 WHO 分类的。
术前 Ki-67 指数可能为滤泡性甲状腺肿瘤的一部分患者提供诊断信息。
