Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17# Panjiayuan Street, Chaoyang District, Beijing, 100021, China.
Endocr Pathol. 2024 Sep;35(3):230-244. doi: 10.1007/s12022-024-09822-3. Epub 2024 Aug 5.
The prognosis of thyroid cancer in patients varies significantly based on different pathological types or distinct clinical situations. Investigating the expression of immune checkpoint molecules PD-L1 and B7-H3 in high-risk thyroid cancer and their correlation with clinicopathological features and prognosis will contribute to the development of novel therapeutic strategies. A retrospective sample of 202 patients with thyroid cancer who underwent surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences was collected, including 33 cases of anaplastic thyroid cancer (ATC), 21 cases of differentiated thyroid cancer (DTC) with distant metastasis (DM), 7 cases of differentiated high-grade thyroid carcinoma (DHGTC), and 109 cases of aggressive subtypes of papillary thyroid carcinoma (PTC) (including 28 cases of tall cell PTC, 31 cases of diffuse sclerosing PTC, 20 cases of solid PTC, 15 cases of columnar cell PTC, and 15 cases of hobnail PTC). In the control group, there were 32 cases of classic PTC. The differences in protein expression between PD-L1 and B7-H3 in several high-risk thyroid cancers and normal tissues and controls were compared by immunohistochemical staining, and the clinicopathological features and prognostic relevance were statistically analyzed. The expression of PD-L1 in ATC (P < 0.001), tall cell PTC (P = 0.031), and DHGTC (P = 0.003) was significantly higher than that in classic PTC. The expression of B7-H3 in ATC (P < 0.001), DTC with DM (P = 0.001), diffuse sclerosing PTC (P = 0.013), columnar cell PTC (P = 0.007), solid PTC (P < 0.001), hobnail PTC (P < 0.001), and DHGTC (P < 0.001) was significantly higher than that in classic PTC. In ATC, PD-L1 expression correlated significantly with extrathyroidal extension (ETE) (P = 0.027) and B7-H3 expression correlated significantly with male patients (P = 0.031) and lymph node metastasis (LNM) (P = 0.026). The positive expression of B7-H3 (P = 0.041) was an independent risk factor for disease progression in ATC. B7-H3 positive expression (P = 0.049), PD-L1 positive expression (P = 0.015), and tumor diameter ≥ 2 cm (P = 0.038) were independent risk factors for disease progression in patients with DTC with DM. PD-L1 positive expression (P = 0.019) and tumor diameter ≥ 2 cm (P = 0.018) were independent risk factors for disease progression in patients with aggressive subtypes of PTC. B7-H3 and PD-L1 are expected to be effective prognostic indicators for patients with aggressive thyroid cancer, which can help in optimization of individualized treatment strategies. Immunotherapy targeting these two molecules may provide new and complementary ideas for the treatment of high-risk/refractory thyroid cancer.
甲状腺癌患者的预后因不同的病理类型或不同的临床情况而有显著差异。研究免疫检查点分子 PD-L1 和 B7-H3 在高危甲状腺癌中的表达及其与临床病理特征和预后的相关性，将有助于开发新的治疗策略。本研究回顾性分析了 202 例在中国医学科学院肿瘤医院接受手术治疗的甲状腺癌患者的样本，包括 33 例间变性甲状腺癌（ATC）、21 例远处转移的分化型甲状腺癌（DTC）、7 例高级别分化型甲状腺癌（DHGTC）和 109 例侵袭性亚型乳头状甲状腺癌（PTC）（包括 28 例高细胞 PTC、31 例弥漫性硬化型 PTC、20 例实体 PTC、15 例柱状细胞 PTC 和 15 例鞋钉样 PTC）。在对照组中，有 32 例经典型 PTC。通过免疫组织化学染色比较 PD-L1 和 B7-H3 在几种高危甲状腺癌和正常组织及对照组中的蛋白表达差异，并进行统计学分析临床病理特征和预后相关性。ATC（P<0.001）、高细胞 PTC（P=0.031）和 DHGTC（P=0.003）中 PD-L1 的表达明显高于经典型 PTC。ATC（P<0.001）、DTC 伴远处转移（P=0.001）、弥漫性硬化型 PTC（P=0.013）、柱状细胞 PTC（P=0.007）、实性 PTC（P<0.001）、鞋钉样 PTC（P<0.001）和 DHGTC（P<0.001）中 B7-H3 的表达明显高于经典型 PTC。在 ATC 中，PD-L1 表达与甲状腺外侵犯（ETE）显著相关（P=0.027），B7-H3 表达与男性患者（P=0.031）和淋巴结转移（LNM）（P=0.026）显著相关。B7-H3 阳性表达（P=0.041）是 ATC 疾病进展的独立危险因素。B7-H3 阳性表达（P=0.049）、PD-L1 阳性表达（P=0.015）和肿瘤直径≥2cm（P=0.038）是 DTC 伴远处转移患者疾病进展的独立危险因素。PD-L1 阳性表达（P=0.019）和肿瘤直径≥2cm（P=0.018）是侵袭性 PTC 患者疾病进展的独立危险因素。B7-H3 和 PD-L1 有望成为评估侵袭性甲状腺癌患者预后的有效指标，有助于优化个体化治疗策略。针对这两个分子的免疫治疗可能为高危/难治性甲状腺癌的治疗提供新的、互补的思路。
