Lin28A and androgen receptor expression in ER-/Her2+ breast cancer

Breast Cancer Res Treat. 2016 Feb;156(1):135-47. doi: 10.1007/s10549-016-3744-9. Epub 2016 Mar 5.

Abstract

The aim of this study was to examine the expression of Lin28A and androgen receptor (AR) in ER-/Her2+ breast cancer, and to research the association of Lin28A and AR co-expression status with patients' prognosis. The expression of Lin28A and AR in formalin-fixed and paraffin-embedded surgical sections from 305 patients with ER-/Her2+ breast cancer was analyzed by immunohistochemistry, and the co-expression patterns in breast cancer cells were investigated by immunofluorescent staining. The impact of the expression of Lin28A and AR in prognosis was also assessed by the Kaplan-Meier, univariate, and multivariate logistic regression models. This study included 305 cases ER-/Her2+ breast cancer patients. Lin28A and AR were expressed in 240 cases (78.7 %) and 220 cases (72.1 %), respectively. Lin28A tended to be higher in AR-positive patients (75.0 %). Lin28A and AR co-expression (Lin28+/AR+) was significantly associated with high tumor grade (G3) (p = 0.023) and high Ki67 index (p = 0.020). The mRNA and protein expression levels of Lin28A and AR were higher in MDA-MB-453 cells (ER-/Her2+) than in the MDA-MB-231 cells (ER-/Her2-). In univariate analysis, Lin28A+/AR+ was significant risk factors associated with unfavorable OS (p = 0.049) and RFS (p = 0.019). Kaplan-Meier analysis showed that Lin28A+/AR+ expression showed lower RFS rates compared with Lin28A-/AR+ (p = 0.043) and Lin28A-/AR- patients(p = 0.019). Multivariate cox model showed that Lin28A+/AR+ remained an independent negative prognostic factor for RFS. Our study showed that Lin28A and AR co-expressed in ER-/Her-2+ breast cancer and correlated with poor prognosis. The possibility that Lin28A may drive AR expression via a positive feedback mechanism remains to be tested.

Keywords: Androgen receptor; Breast cancer; ER; Her-2; Lin28A; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Female
  • Humans
  • Neoplasm Grading
  • Prognosis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Receptors, Estrogen / deficiency*
  • Regression Analysis

Substances

  • AR protein, human
  • LIN28B protein, human
  • RNA-Binding Proteins
  • Receptors, Androgen
  • Receptors, Estrogen
  • ERBB2 protein, human
  • Receptor, ErbB-2