Prognostic value of follistatin-like 3 in human invasive breast cancer

Oncotarget. 2017 Jun 27;8(26):42189-42197. doi: 10.18632/oncotarget.15026.


Follistatin-like 3 (FSTL3) binds and inactivates activin, a growth factor involved with cell growth and differentiation. We have previously shown FSTL3 overexpression in invasive breast cancers, but its clinical relevance remained unexplored. Here we evaluate FSTL3 as a prognostic tool and its relation with clinical and pathological features of breast cancer. A cohort of 154 women diagnosed with invasive breast cancer between 2008 and 2012 was followed up for 5 years. Tumor samples were processed by immunohistochemistry to detect FSTL3 expression in tumor epithelium. FSTL3 expression was classified semiquantitatively and tested for possible correlation with age, menopause status, stage, tumor histological type and grade, estrogen receptor, progesterone receptor, and HER2 expression. Survival plots with Kaplan-Mayer statistics were used to assess whether FSTL3 expression predicted disease-free survival. Our findings show that FSTL3 staining was unrelated to menopausal status, histological type, disease stage, or receptor profile. However, the intensity of FSTL3 immunostaining correlated inversely with tumor size (r = -0.366, p<0.001) and with nuclear grade (p<0.01). The intensity of FSTL3 expression in the tumoral epithelium was not predictive of the disease-free survival (p = 0.991, log-rank test), even though the follow-up length and the study size were sufficient to detect a significant reduction in disease-free survival among women with stage III-IV compared to stage I-II disease (p<0.001). FSTL3 expression in invasive breast cancer is inversely associated with tumor size and nuclear grade but it does not predict disease relapse in the short term.

Keywords: FLRG; FSTL3; activin; breast cancer; follistatin.

MeSH terms

  • Biomarkers, Tumor*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Female
  • Follistatin-Related Proteins / genetics*
  • Follistatin-Related Proteins / metabolism
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Odds Ratio
  • Prognosis
  • Risk Factors


  • Biomarkers, Tumor
  • Follistatin-Related Proteins
  • Fstl3 protein, human