Molecular markers for reinforcement of histological subclassification of neuroendocrine lung tumors
Molecular markers for reinforcement of histological subclassification of neuroendocrine lung tumors
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DOI：
10.1111/j.1349-7006.2004.tb03212.x
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发表时间：
2004-04
期刊：
影响因子：
5.7
通讯作者：
Yasuhito Kobayashi;Y. Tokuchi;T. Hashimoto;M. Hayashi;H. Nishimura;Y. Ishikawa;K. Nakagawa;Y. Sato;Atsushi Takahashi;E. Tsuchiya
中科院分区：
文献类型：
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作者：
Yasuhito Kobayashi;Y. Tokuchi;T. Hashimoto;M. Hayashi;H. Nishimura;Y. Ishikawa;K. Nakagawa;Y. Sato;Atsushi Takahashi;E. Tsuchiya
神经内分泌肺肿瘤（内斯）的恶性程度按以下顺序增加：从典型类癌（TC）到非典型类癌（AC），再到大细胞神经内分泌癌（LCNEC）和小细胞肺癌（SCLC）。然而，组织学分类有时被证明是困难的。我们在57例内斯（19例TC、5例AC、14例LCNEC和19例SCLC）中使用8个微卫星标记和免疫组化方法研究了杂合性丢失（洛）和p53、Bcl-2和Bax蛋白的表达，寻找客观的遗传标记来区分亚型。D3 S1300、RB 12和TP 53的LOH频率、RB 12和TP 53的洛状态组合以及化学染色证实的Bcl-2/Bax比值和p53阳性率在组织病理学诊断的内斯中显著不同。参考D3 S1300、RB 1 2和TP 53上的洛杂合性缺失以及RB 1 2和TP 53上的联合洛杂合性缺失状态（即，两个洛（-）对一个洛（+））。为了比较AC和LCNEC+SCLC之间的差异，应用TP 53上的洛或两个标记物的组合-一个洛（+）与两个洛（+）-。此外，在3例基于组织学和洛缺失标记诊断不一致的病例中，生存分析认为后者的诊断可能性更大。目前的研究表明，使用微卫星标记评估LOH可以提供客观的标记，可以区分亚型的内斯，组织学评估通常会导致分歧。
The degree of malignancy of neuroendocrine lung tumors (NEs) increases in this order: from typical carcinoids (TCs) through atypical carcinoids (ACs) to large cell neuroendocrine carcinomas (LCNECs) and small cell lung carcinomas (SCLCs). However, histological classification has sometimes proved difficult. We here investigated loss of heterozygosity (LOH) using eight microsatellite markers and expression of p53, Bcl‐2 and Bax proteins using immunohistochemical methods in 57 NEs (19 TCs, 5 ACs, 14 LCNECs and 19 SCLCs), looking for objective genetic markers to distinguish between subtypes. The frequencies of LOHs on D3S1300, RBi2 and TP53, the combinations of LOH status for RBi2 and TP53, and the immunohistochemically demonstrated Bcl‐2/Bax ratios and p53‐positive rates significantly differed among histopathologically diagnosed NEs. Differentiation between TC and AC was possible with reference to LOH on D3S1300, RBi2 and TP53, and the combined LOH status on RBi2 and TP53 (i.e., both LOH(‐) versus one LOH(+)). For comparison between AC and LCNEC+SCLC, LOH on TP53 or the combination of two markers—one LOH(+) versus both LOH(+)—was applied. Furthermore, in three discordant cases of diagnoses based on histology and LOH markers, diagnoses using the latter were considered to be more probable by survival analysis. The present study indicated that assessment of LOHs using microsatellite markers could provide objective markers that can distinguish subtypes of NEs, for which histological assessment may commonly result in disagreement.