Altered Expression of Cell Cycle-Regulatory Tumor Suppressor Proteins in Neuroendocrine Lung tumors : Their Significance for the Differential Diagnosis

神经内分泌肺肿瘤中细胞周期调节肿瘤抑制蛋白的表达改变：其鉴别诊断的意义

基本信息

批准号：
11670558
负责人：
AKITA Hirotoshi
金额：
$ 2.11万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670558/
关键词：
Lung Cancer RB p16 肺カルチノイド腫瘍 p16^<NK4A>

项目摘要

Neuroendocrine neoplasms of the lung represent a wide spectrum of phenotypically and biologically distinct entities. Their histopathological diagnosis, which carries therapeutic and prognostic significance, may sometimes be difficult because of their overlapping features. We have previously demonstrated that large cell neuroendocrine carcinomas (LCNECs) and small cell lung cancers (SCLCs) failed to show positive nuclear staining of RB protein (RB-), while typical and atypical carcinoids (TCs and ACs) showed nuclear RB immunostaining (RB+) (Cagle, P.T., et al. Am. J.Pathol., 150 : 393, 1997). In the present study, a series of 58 surgically resected lung tumors, of which 33 tumors were initially diagnosed as SCLCs and 25 as TCs or ACs, were studied for RB and p16 protein expression by immunohistochemistry. They were also reviewed for their pathological diagnosis blinded to the RB and p16 protein status. Nineteen tumors were diagnosed as TCs, five as ACs, seven as LCNECs, and 27 as SCLCs. Three of seven LCNECs were RB+, while the other four were RB-. In contrast, all 19 TCs were RB+ and all 27 SCLCs were RB-. In addition, two of five ACs were RB+, while the other three were RB-. Interestingly, all three RB+ LCNECs and the one RB+ AC tested failed to show nuclear staining of p16 protein in any tumor cells (p16-), although some normal stromal cells showed nuclear staining of p16 protein (p16+) as positive internal controls, indicating loss of p16 function in these tumors. Of note, the three RB+ LCNECs were initially diagnosed as SCLCs and one of the RB- ACs was initially considered to be a TC.With the exception of TCs, tumors were significantly more prevalent in heavy smokers with pack years greater than 20 compared with nonsmokers and light smokers with pack years 【less than or equal】 20 (P<0.01). These findings suggest that all SCLCs and LCNECs have abnormalities in the p16 : RB pathway as do at least certain ACs, whereas the p16 : RB pathway is normal in TCs.

肺的神经内分泌肿瘤代表了广泛的表型和生物学上不同的实体。他们的组织病理学诊断具有热和预后意义，由于其重叠特征，有时可能很困难。我们先前已经证明，大型细胞神经内分泌癌（LCNEC）和小细胞肺癌（SCLC）未能显示RB蛋白（RB-）的阳性核染色，而典型的和异型的类癌（TCS和ACS）显示了核RB免疫染色（RB+）（RB+）（rb+）（cagle）（cagle）（cagle，p.t。 1997）。在本研究中，研究了一系列58种手术切除的肺肿瘤，其中33个肿瘤最初被诊断为SCLC，而25个肿瘤通过免疫组织化学研究了RB和P16蛋白表达的TC或ACS。还对他们的病理诊断对RB和p16蛋白质状态视而不见。诊断为19个肿瘤为TCS，5个为AC，7个为LCNEC，27个为SCLC。七个LCNEC中有三个是RB+，而其他四个是RB-。相比之下，所有19个TC均为RB+，所有27个SCLC均为RB-。此外，五个AC中的两个是RB+，而其他三个为RB-。有趣的是，尽管所有肿瘤细胞（p16-）中，所有三个RB+ LCNEC和一个RB+ AC测试均未显示p16蛋白的核染色，尽管一些正常的基质细胞显示p16蛋白（p16+）的核染色是阳性的内部对照，表明这些肿瘤中p16的功能丧失。值得注意的是，最初将三个RB+ LCNEC诊断为SCLC，其中一个RB-ACS最初被认为是TC。除TC外，肿瘤在不超过20岁以上的人群中的沉重吸烟者中的肿瘤明显更为普遍，与非烟雾者和轻度吸烟者相比，具有少于或少于或等于或同样的吸烟者[P <0.01）（P <0.01）。这些发现表明，所有SCLC和LCNEC在p16：rb途径中都具有异常，至少像某些AC一样，而p16：rb途径在TC中是正常的。