Loss of FAT1 during the progression from DCIS to IDC and predict poor clinical outcome in breast cancer

Exp Mol Pathol. 2016 Feb;100(1):177-83. doi: 10.1016/j.yexmp.2015.12.012. Epub 2015 Dec 22.

Abstract

FAT1 and β-catenin are important tumor regulatory factors. The aim of this study was to detect the possible disparity in their expression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) and to explore its correlation with clinicopathological factors. We used immunohistochemistry to detect protein expression of FAT1 and β-catenin in breast cancer tissues from 113 cases of DCIS and 149 cases of IDC. As compared with DCIS, expression of FAT1 and β-catenin were significantly decreased in IDC (P<0.05). In addition, our study also revealed a correlation between their expression and some clinicopathological factors. We found that FAT1 expression was associated with nuclear grade and comedonecrosis (P<0.05) in DCIS, whereas FAT1 expression showed significant variation with histological grade and LN status (P<0.05) in IDC. Similar associations were observed in the β-catenin subgroup. Furthermore, expressions of FAT1 and β-catenin were correlated with each other in DCIS and IDC (P<0.05). FAT1(-), β-catenin(-), or FAT1(-)/β-catenin(-) may indicate worse DFS and OS in breast cancer (P<0.05). This study suggests that loss of FAT1 and β-catenin are associated with breast cancer progression, aggressive behavior, and poor prognosis. FAT1 alone or together with β-catenin might be a valuable biomarker in predicting the prognosis of patients with breast cancer.

Keywords: Breast cancer; Ductal carcinoma in situ; FAT1; Invasive ductal carcinoma; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cadherins / genetics*
  • Carcinoma, Ductal, Breast / diagnosis
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Intraductal, Noninfiltrating / genetics
  • Carcinoma, Intraductal, Noninfiltrating / metabolism
  • Carcinoma, Intraductal, Noninfiltrating / pathology*
  • Carcinoma, Intraductal, Noninfiltrating / therapy
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Middle Aged
  • Receptors, Estrogen / metabolism
  • Treatment Outcome
  • beta Catenin / metabolism

Substances

  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • Cadherins
  • FAT1 protein, human
  • Receptors, Estrogen
  • beta Catenin