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TROP2 在非小细胞肺癌中的临床影响及其与异常 p53 核聚集的相关性。

Clinical impact of TROP2 in non-small lung cancers and its correlation with abnormal p53 nuclear accumulation.

机构信息

Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

出版信息

Pathol Int. 2020 May;70(5):287-294. doi: 10.1111/pin.12911. Epub 2020 Feb 10.

Abstract

Tumor-associated calcium signal transducer 2 (TROP2) is a cell-surface glycoprotein involved in the high malignant potential of several cancers. Antibody-drug conjugates that target TROP2 represent a promising approach for the treatment of TROP2-expressing cancers including lung cancer and breast cancer. TROP2 expression was tested by immunohistochemistry in lung adenocarcinoma (ADC) and squamous cell carcinoma samples, and its correlation with clinicopathological factors, including survival rate and p53 mutation, was statistically analyzed. We found that increased TROP2 expression was significantly associated with a poor clinical course in patients with ADC, but not in patients with squamous cell carcinoma. A more significant association with poor outcome was seen in ADC cases with a high histological grade as well as those without the epidermal growth factor receptor (EGFR) mutation. A significant correlation between TROP2 expression and abnormal p53 nuclear accumulation/expression was also found in ADC. In the present study, we discovered a significant correlation between TROP2 expression and p53 mutation in ADC, and that TROP2 expression was a prognostic factor in ADC cases with a high histological grade as well as those without the EGFR mutation. Signals mediated by mutated p53 might influence TROP2 expression in ADC.

摘要

肿瘤相关钙信号转导蛋白 2(TROP2)是一种细胞表面糖蛋白,参与多种癌症的高恶性潜能。靶向 TROP2 的抗体药物偶联物代表了治疗 TROP2 表达癌症的一种很有前途的方法,包括肺癌和乳腺癌。通过免疫组织化学检测肺腺癌(ADC)和鳞状细胞癌样本中的 TROP2 表达,并对其与临床病理因素(包括生存率和 p53 突变)的相关性进行统计学分析。我们发现,TROP2 表达增加与 ADC 患者的不良临床病程显著相关,但与鳞状细胞癌患者无关。在组织学分级较高的 ADC 病例以及无表皮生长因子受体(EGFR)突变的病例中,与不良预后的相关性更为显著。在 ADC 中还发现 TROP2 表达与异常 p53 核聚集/表达之间存在显著相关性。在本研究中,我们发现 TROP2 表达与 ADC 中的 p53 突变之间存在显著相关性,并且 TROP2 表达是组织学分级较高的 ADC 病例以及无 EGFR 突变的 ADC 病例的预后因素。突变型 p53 介导的信号可能影响 ADC 中 TROP2 的表达。

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