Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden.
Endocr Pathol. 2022 Jun;33(2):231-242. doi: 10.1007/s12022-022-09714-4. Epub 2022 Mar 19.
Follicular thyroid tumors pose a diagnostic challenge on the preoperative level, as the discrimination between follicular thyroid carcinoma (FTC) and adenoma (FTA) demands careful histopathological investigation. Moreover, prognostication of FTCs is mostly based on tumor size and extent of invasive properties, while immunohistochemical markers pinpointing high-risk cases are lacking. We have routinely established a Ki-67 labeling index for follicular thyroid tumors since 1999. To assess the potential value of Ki-67 as an adjunct tool to (1) correctly separate FTCs from FTAs and (2) help identify poor-prognosis FTCs, we collected histopathological and clinical data from 818 follicular thyroid tumors with a histological Ki-67 labeling index established in clinical routine practice (516 FTAs, 252 FTCs, and 50 follicular thyroid tumors of uncertain malignant potential (FT-UMPs)). The Ki-67 labeling index was higher in FTCs (mean 5.8%) than in FTAs (mean 2.6%) (P < 0.001), and a receiver operating characteristic curve analysis revealed a cut-off value of 4% to separate FTC from FTA with a sensitivity and specificity of 65% and 83%, respectively. Similarly, a Ki-67 labeling index above 4% was found to identify FTCs that later metastasized from clinically indolent FTCs with a sensitivity and specificity of 80% and 48%, respectively. Ki-67 constituted an independent predictor of future FTC metastases/recurrence and death of disease, and a value > 4% was a reliable prognostic marker within individual pT staging groups. We conclude that Ki-67 is a potentially valuable marker for the prognostication of FTCs, and future implementation in the histopathological assessments of follicular thyroid tumors could be beneficial if reproduced in international series.
滤泡性甲状腺肿瘤在术前诊断具有挑战性，因为区分滤泡性甲状腺癌（FTC）和腺瘤（FTA）需要仔细的组织病理学研究。此外，FTC 的预后主要基于肿瘤大小和侵袭性程度，而缺乏指出高风险病例的免疫组织化学标志物。自 1999 年以来，我们常规建立了滤泡性甲状腺肿瘤的 Ki-67 标记指数。为了评估 Ki-67 作为辅助工具的潜在价值，（1）正确区分 FTC 和 FTA，（2）帮助识别预后不良的 FTC，我们收集了 818 例滤泡性甲状腺肿瘤的组织病理学和临床数据，这些肿瘤的 Ki-67 标记指数是在临床常规实践中建立的（516 例 FTA、252 例 FTC 和 50 例滤泡性甲状腺肿瘤恶性潜能不确定（FT-UMP））。FTC 的 Ki-67 标记指数（平均 5.8%）高于 FTA（平均 2.6%）（P<0.001），ROC 曲线分析显示，4%的 Ki-67 标记指数可用于区分 FTC 和 FTA，敏感性和特异性分别为 65%和 83%。同样，Ki-67 标记指数>4%可用于识别后来发生转移/复发的临床惰性 FTC 中的 FTC，敏感性和特异性分别为 80%和 48%。Ki-67 是 FTC 转移/复发和疾病死亡的独立预测因子，在个体 pT 分期组内，>4%的值是可靠的预后标志物。我们得出结论，Ki-67 是 FTC 预后的一个有潜力的标志物，如果在国际系列中得到复制，未来在滤泡性甲状腺肿瘤的组织病理学评估中的实施可能是有益的。
