Prognostic Significance of Phosphorylated Fyn in Patients with Lung Adenocarcinoma after Lung Resection

Ann Thorac Cardiovasc Surg. 2019 Oct 20;25(5):246-252. doi: 10.5761/atcs.oa.19-00078. Epub 2019 Jun 12.

Abstract

Purpose: Src family tyrosine kinases, including Fyn, are non-receptor tyrosine kinases that drive malignancy in various kinds of cancers. Fyn has also been suggested to be an effector of epidermal growth factor receptor (EGFR) signaling, and is recognized as a potential therapeutic target. However, little is known about the clinical importance of phosphorylated Fyn (pFyn) in lung adenocarcinoma. The purpose of this study is to examine the prognostic significance of pFyn in this disease.

Methods: A total of 282 lung adenocarcinoma specimens were collected from patients who underwent surgery at our institute. A tissue microarray was assembled from paraffin-embedded tumor blocks. pFyn expression was analyzed through immunostaining of the tissue microarray and each case was classified as positive or negative. The association of clinical information with pFyn expression was analyzed statistically.

Results: pFyn was positive in 107 cases. A pFyn-positive status was significantly associated with male gender, p53 mutant, pathological stage, tumor size, plural invasion, lymphatic invasion, vascular invasion, and differentiation. pFyn positivity was associated with poor relapse-free survival (RFS; hazard ratio [HR]: 2.11, 95% confidence interval [CI]: 1.32-3.42, p <0.01) and poor overall survival (OS; HR: 1.95, 95% CI: 1.17-3.33, p = 0.01).

Conclusion: pFyn expression may affect the prognosis of patients with lung adenocarcinoma after lung resection.

Keywords: immunohistochemistry; lung adenocarcinoma; phosphorylated Fyn; survival analysis.

MeSH terms

  • Adenocarcinoma of Lung / enzymology*
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / mortality
  • Adenocarcinoma of Lung / surgery
  • Aged
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Mutation
  • Phosphorylation
  • Pneumonectomy* / adverse effects
  • Pneumonectomy* / mortality
  • Progression-Free Survival
  • Proto-Oncogene Proteins c-fyn / analysis*
  • Proto-Oncogene Proteins c-fyn / genetics
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Tissue Array Analysis
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • FYN protein, human
  • Proto-Oncogene Proteins c-fyn