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.

肺部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，其组织病理学诊断具有治疗和预后意义，但由于其重叠特征有时可能很困难。小细胞肺癌 (SCLC) 未显示 RB 蛋白 (RB-) 核染色阳性，而典型和非典型类癌 (TC 和 AC) 则显示核 RB免疫染色 (RB+) (Cagle, P.T., et al. Am. J. Pathol., 150: 393, 1997) 在本研究中，一系列 58 个手术切除的肺部肿瘤，其中 33 个肿瘤最初被诊断为 SCLC，通过免疫组织化学研究了 25 个 TC 或 AC 的 RB 和 p16 蛋白表达，并对其病理诊断进行了回顾。对 RB 和 p16 蛋白状态不知情的肿瘤被诊断为 TC，5 个为 AC，7 个为 LCNEC，27 个为 SCLC。7 个 LCNEC 中的 3 个为 RB+，而其他 4 个为 RB-。均为 RB+，所有 27 个 SCLC 均为 RB-。此外，5 个 AC 中有 2 个为 RB+，另外 3 个为 RB-。 RB+ LCNEC 和测试的一个 RB+ AC 未能在任何肿瘤细胞 (p16-) 中显示 p16 蛋白的核染色，尽管一些正常基质细胞显示 p16 蛋白 (p16+) 的核染色作为阳性内部对照，表明 p16 功能丧失值得注意的是，三个 RB+ LCNEC 最初被诊断为 SCLC，其中一个 RB-AC 最初被认为是 TC。与不吸烟者和吸烟年数【小于或等于】20 的轻度吸烟者相比，吸烟年数大于 20 的重度吸烟者中 TC、肿瘤的发生率显着更高（P<0.01）。这些结果表明，所有 SCLC 和 LCNEC 均存在异常。 p16 : RB 通路至少与某些 AC 一样，而 p16 : RB 通路在 TC 中是正常的。