文章：

肺混合性神经内分泌癌与“所谓报道的组织学转化”之间关系的克隆性分析

Clonality Analysis for the Relationship between the Pulmonary Combined Neuroendocrine Carcinoma and “the So-Called Reported Histologic Transformation”

原文发布日期：29 November 2023

DOI: 10.3390/cancers15235649

类型: Article

开放获取: 是

英文摘要：

Histologic transformation (HT) is common following targeted therapy in adenocarcinoma. However, whether the transformed tumor is a new component or a combined neuroendocrine carcinoma (C-NEC) remains controversial. We aimed to explore the relationship between pulmonary C-NEC and HT. Macro-dissection was performed on different components of surgically resected C-NEC samples. Molecular alterations and clonal evolution were analyzed using whole exome sequencing (WES). The gene statuses forTP53andRB1were determined using immunohistochemistry (IHC) and WES to analyze the relationship between C-NEC and reported HT. Sixteen combined small-cell lung cancer patients and five combined large-cell neuroendocrine carcinoma patients were enrolled. The frequency of p53 and Rb inactivation, assessed using IHC in NEC and non-NEC components, was 76.2/76.2% and 66.7/61.9%, respectively. The expression consistency between the components was 81.0 and 85.7% for p53 and Rb, respectively. The frequencies ofTP53,RB1, andEGFRmutations, assessed using WES in NEC and non-NEC components, were 81.0/81.0%, 28.6/28.6%, and 42.9/42.9%, respectively. The concordance rates forTP53,RB1, andEGFRwere 90.5, 71.4, and 90.5%, respectively. The consistency rate between IHC and WES was 81.0 and 61.9% forTP53andRB1, respectively. The different components had a common clonal origin for the 21 C-NECs in the clonal analysis, consistent with previous studies on HT. Our study shows that IHC is more sensitive for Rb detection and C-NEC, and the reported HT may be due to differences in evaluations between pathologist and clinicians. Assessing the p53/Rb andEGFRstatus for such cases would help in recognizing potential transformation cases or uncovering potential combined components.

摘要翻译： 

组织学转化在腺癌靶向治疗后较为常见。然而，转化后的肿瘤究竟是新生成分还是复合性神经内分泌癌仍存在争议。本研究旨在探讨肺复合性神经内分泌癌与组织学转化之间的关系。我们对手术切除的复合性神经内分泌癌样本中不同成分进行宏观分离，并通过全外显子测序分析分子改变与克隆演化。采用免疫组化与全外显子测序检测TP53和RB1基因状态，以分析复合性神经内分泌癌与已报道组织学转化的关联。研究纳入16例复合性小细胞肺癌患者及5例复合性大细胞神经内分泌癌患者。免疫组化检测显示，神经内分泌癌成分与非神经内分泌癌成分中p53与Rb失活频率分别为76.2%/76.2%和66.7%/61.9%，两种成分间p53与Rb表达一致性分别为81.0%和85.7%。全外显子测序分析显示，TP53、RB1及EGFR突变在两种成分中的频率分别为81.0%/81.0%、28.6%/28.6%和42.9%/42.9%，其一致性分别为90.5%、71.4%和90.5%。免疫组化与全外显子测序对TP53和RB1检测的一致性分别为81.0%和61.9%。克隆分析表明21例复合性神经内分泌癌的不同成分具有共同克隆起源，这与既往组织学转化研究结果一致。本研究表明免疫组化对Rb检测及复合性神经内分泌癌诊断更具敏感性，已报道的组织学转化可能源于病理学家与临床医生评估标准的差异。对此类病例进行p53/Rb及EGFR状态评估，将有助于识别潜在转化病例或发现潜在的复合成分。

原文链接：

Clonality Analysis for the Relationship between the Pulmonary Combined Neuroendocrine Carcinoma and “the So-Called Reported Histologic Transformation”