甲状腺滤泡癌组织中PD-L1与dMMR相关蛋白表达的关系及其临床意义

Correlation between the expression of PD-L1 and dMMR related proteins in follicular thyroid carcinoma tissues and its clinical significance

目的:探讨甲状腺滤泡癌组织中PD-L1与dMMR相关蛋白表达的关系及其临床意义。方法:收集2015年1月至2020年6月福建医科大学附属第二医院60例甲状腺滤泡癌患者的癌组织蜡块,再次经H-E染色确诊,采用免疫组化法检测癌组织和癌旁组织中PD-L1的表达以及MMR系统4个基因(MLH1、MSH2、MSH6、PMS2)编码的4种同源蛋白表达情况,分析甲状腺滤泡癌组织中PD-L1表达与MMR相关蛋白缺失的关系及其临床意义。结果:60例甲状腺滤泡癌组织中,PD-L1表达率显著高于癌旁组织[(63.3%(38/60) vs 11.7%(7/60),P<0.05)];PD-L1的表达与肿瘤的直径、甲状腺外浸润、血管侵犯、复发与否具有显著相关性(均P<0.05)。60例患者癌组织标本中,24(40.0%)例患者4种MMR相关蛋白均有表达,为pMMR肿瘤;36(60.0%)例出现1种或多种MMR相关蛋白表达缺失,为d MMR肿瘤。d MMR型甲状腺滤泡癌与患者有无淋巴结转移和肿瘤分期有显著相关性(均P<0.05)。PD-L1与d MMR发生率成正相关,前者是肿瘤复发的独立风险因素,后者与患者有更好的预后相关。PD-L1+/pMMR患者与肿瘤更高恶性程度相关,而PD-L1+/dMMR患者与肿瘤病理特征无关,但可能容易从免疫治疗中获益。结论:PD-L1阳性表达及dMMR在甲状腺滤泡癌中有较高的发生率,前者与肿瘤侵袭性增加相关,且是肿瘤复发的独立风险因素,而后者是甲状腺滤泡癌发生过程中的早期分子事件,且与患者有更好的预后相关。

Objective: To investigate the correlation between PD-L1 expression and dMMR related proteins in follicular thyroid carcinoma tissues and its clinical significance. Methods: The postoperative paraffin-embedded tissue samples from 60 patients with thyroid follicular carcinoma were collected from the Second Affiliated Hospital of Fujian Medical University during January 2015 and June 2020. The collected samples were re-confirmed as thyroid follicular carcinoma tissues by Hematoxylin-eosin staining. The expression of PD-L1 and four homologous proteins encoded by four genes(MLH1, MSH2, MSH6, PMS2) in MMR system were detected by immunohistochemistry in the cancer and paracancerous tissues. The relationship between the expression of PD-L1 and depletion of MMR related proteins in thyroid follicular carcinoma tissues and its clinical significance were analyzed. Results: The positive expression rate of PD-L1 was significantly higher in the follicular thyroid carcinoma tissues than that in paracancerous tissues[63.3%(38/60) vs 11.7%(7/60), P<0.05]. The expression of PD-L1 was significantly correlated with tumor diameter, extrathyroidal infiltration, vascular invasion and recurrence(all P<0.05). In the cancer tissue specimens from 60 patients, 24(40.0%) had expression of four MMR related proteins, which were pMMR tumors, and 36(60.0%) had depletion of one or more MMR related proteins, which were dMMR tumors. The dMMR-type thyroid follicular carcinoma was significantly correlated with the status of lymph node metastasis and tumor staging(all P<0.05). PD-L1 was positively correlated with the incidence of dMMR, and PD-L1 was an independent risk factor for disease recurrence, while d MMR was associated with a better prognosis. Patients with PD-L1+/pMMR type were associated with higher tumor malignancy, while patients with PD-L1+/dMMR type were not associated with tumor pathological features but may easily benefit from immunotherapy. Conclusion: Positive PD-L1 expression and dMMR highly occur in follicular thyroid carcinoma. PD-L1 is associated with the increased tumor invasion and is an independent risk factor for disease recurrence,while dMMR is an early molecular event in the development of thyroid follicular carcinoma and is associated with better prognosis of patients.