[Aberrant Expression of Rb and pRb-780, pRb-795 in Lung Adenocarcinoma Patients with EGFR Mutations and Their Clinical Significance]

Zhongguo Fei Ai Za Zhi. 2017 May 20;20(5):312-317. doi: 10.3779/j.issn.1009-3419.2017.05.03.
[Article in Chinese]

Abstract

Background: Rb is an important tumor suppressor gene that regulates cell cycle progression. Rb dysfunction can lead to over proliferation of cells and lead to the occurrence of tumor. Loss or reduced Rb expression as well as over phosphorylation of Rb are important mechanisms of Rb dysfunction. The mutated epidermal growth factor receptor (EGFR) gene is an important driver gene in lung adenocarcinoma, and plays an important role in the development of lung cancer. The purpose of this study was to investigate the status of Rb in lung adenocarcinoma patients with EGFR mutations and define the clinicopathologic features.

Methods: 23 cases pulmonary adenocarcinoma patients with EGFR mutations were collected. The status of Rb and pRb-780, pRb-795 were determined byimmunohistochemistry.

Results: Loss or reduced Rb expression were detected in 16 of 23 samples (69.6%). pRb-780 and pRb-795 over-expressed were identified in 17 (73.9%) and 16 (69.6%) of 23 samples respectively. All the 23 patients had showed loss/reduced Rb expression or over-expressed Rb phosphorylation. Further analysis showed that over expression of pRb-780 and pRb-795 occurred more frequently in advanced patients.

Conclusions: Aberrant expressionof Rb is frequently occurred in lung adenocarcinoma patients with EGFR mutations and may be an important pathogenesis in patients with lung adenocarcinoma. .

背景与目的 Rb作为重要的抑癌基因,调控细胞周期的进程。各种原因导致的Rb功能异常均可导致细胞的持续过度增殖从而导致肿瘤的发生。Rb蛋白表达缺失或减弱及过度磷酸化是Rb功能异常的重要机制。具有突变的表皮生长因子受体(epidermal growth factor receptor, EGFR)基因是肺腺癌重要的驱动基因,在肺癌的发生发展中起着重要的作用。本研究目的在于探讨Rb在EGFR突变的肺腺癌中的存在状态。方法 取23例具有EGFR突变的肺腺癌标本,用免疫组化的方法分析Rb、pRb-780、pRb-795表达状态及临床特征。结果 在23例EGFR突变的肺腺癌患者中Rb蛋白表达缺失/减弱频率为69.6%,pRb-780、pRb-795过表达的频率分别为73.9%、69.6%。23例患者均存在Rb表达缺失/减弱或Rb过度磷酸化。进一步分析发现,pRb-780过表达在晚期患者中发生更多(P=0.022);pRb-795过表达在晚期患者中发生更多,但无统计学差异(P=0.074)。结论 在EGFR突变的肺腺癌患者中,频繁发生Rb的表达缺失/减弱或过度磷酸化,Rb功能异常是EGFR突变肺腺癌患者重要的发病机制。.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Male
  • Middle Aged
  • Mutation
  • Phosphorylation
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*

Substances

  • Retinoblastoma Protein
  • ErbB Receptors

Grants and funding

本研究受国家自然科学基金(No. 81172233、No. 81372306)、天津自然科学基金重点项目(No.16JCZDJC34200)、天津自然科学基金项目(No.13JCYBJC22600)、天津市创新平台专项市级重点实验室建设项目(No.16PTSYJC00160)教育部博士点基金(No.20131202110004)的资助