[Clinicopathological and prognostic significance of a panel of tumor biomarkers in lung adenocarcinoma: a tissue microarray study]

Zhongguo Fei Ai Za Zhi. 2014 Mar;17(3):243-53. doi: 10.3779/j.issn.1009-3419.2014.03.11.
[Article in Chinese]

Abstract

Background: Lung adenocarcinoma is one of the most common histological subtypes of lung cancer. The incidence of this disease was continuously increased. This study aims to detect the expressions of Napsin A, TTF-1, ERCC1, RRM1, EGFR, HER2, ERα, ERβ, PR, and Bcl-2 in lung adenocarcinoma and to explore their correlations with clinicopathological characteristics and prognosis.

Methods: A total of 227 lung adenocarcinoma specimens were constructed in tissue microarrays. The expressions of the 10 tumor biomarkers were analyzed by immunohistochemistry on paraffin-embedded sections.

Results: Among the 10 markers, Napsin A was gender-related (P=0.049). Napsin A, PR, and EGFR were significantly associated with smoking. TTF-1 and ERCC1 were closely associated with tumor size. Napsin A, TTF-1, ERα, and PR were remarkably associated with tumor differentiation. TTF-1, Bcl-2, and ERCC1 were closely associated with tumor stage (P<0.05). No marker was related to age. No correlations were observed between ERβ, HER2, and RRM1 expressions and clinicopathological parameters (P>0.05). Univariate analysis results showed that Napsin A, TTF-1, and ERCC1 were significantly associated with overall survival. TTF-1 was remarkably associated with disease-free survival (P<0.05). Stage I cases were further analyzed and revealed that only Napsin A expression was associated with overall survival (P<0.05). No marker was correlated with disease-free survival (P>0.05). Multivariate analysis results showed that pathological staging was significantly associated with overall survival and disease-free survival (P<0.05). No marker was identified as a predictor of patient outcome (P>0.05).

Conclusions: Napsin A, TTF-1, and ERCC1 are the markers indicating good prognosis of lung adenocarcinoma.

背景与目的 肺腺癌是最常见的肺癌组织学类型,发病率呈上升趋势。本研究旨在探讨Napsin A、TTF-1、ERCC1、RRM1、EGFR、HER2、ERα、ERβ、PR、Bcl-2蛋白在肺腺癌中的表达及与临床病理特征和预后的关系。 方法 将227例肺腺癌石蜡标本构建组织芯片。采用免疫组化方法检测10种靶蛋白标记物在肺腺癌中的表达,分析各蛋白表达与患者临床病理特征和预后的关系。结果 10种蛋白中仅Napsin A蛋白表达与性别有关(P=0.049);Napsin A、PR和EGFR蛋白表达与吸烟有关,TTF-1和ERCC1蛋白表达与肿瘤大小有关,Napsin A、TTF-1、ERα和PR蛋白表达与肿瘤分化程度有关,TTF-1、Bcl-2和ERCC1蛋白表达与病理分期有关(P<0.05)。10种蛋白表达均与年龄无关,ERβ、HER2和RRM1蛋白表达与各项临床病理参数均无相关性(P>0.05)。单因素生存分析显示,Napsin A、TTF-1和ERCC1蛋白表达与患者总生存相关;TTF-1蛋白表达与患者无病生存相关(P<0.05)。进一步分析I期肺腺癌,仅Napsin A蛋白表达与患者总生存相关,P<0.05;10种蛋白表达均与I期患者无病生存无关(P>0.05)。经多因素生存分析,仅病理分期与患者总生存和无病生存相关(P<0.05);10种蛋白表达均未显示与患者生存的相关(P>0.05)。结论 Napsin A、TTF-1和ERCC1蛋白可能是提示肺腺癌患者预后较好的标记物。

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Aspartic Acid Endopeptidases / genetics
  • Biomarkers, Tumor / genetics*
  • DNA-Binding Proteins / genetics
  • Endonucleases / genetics
  • Female
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Transcription Factors

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • TTF1 protein, human
  • Transcription Factors
  • ERCC1 protein, human
  • Endonucleases
  • Aspartic Acid Endopeptidases
  • NAPSA protein, human