Evaluation of Local CYP17A1 and CYP19A1 Expression Levels as Prognostic Factors in Postmenopausal Invasive Ductal Breast Cancer Cases

Biochem Genet. 2016 Dec;54(6):784-802. doi: 10.1007/s10528-016-9756-7. Epub 2016 Jun 30.

Abstract

There is growing attention focused on local estrogen production in the breast tissue and its possible role in breast cancer initiation and progression. Understanding the underlying mechanisms for estrogen synthesis and the microenvironment consisting of tumor and its surrounding adipose tissue might open new avenues in breast cancer prevention, prognosis and treatment. In order to obtain insight, we compared peritumoral and tumor tissue expressions of CYP17A1 and CYP19A1 genes, which play an important role in estrogen biosynthesis. The paired tissue samples of 20 postmenopausal ER+/PR+ patients diagnosed with invasive ductal breast cancer were studied. In addition, 12 breast tissue samples obtained from premenopausal women without a history of breast cancer were also investigated as representative of normal conditions. Peritumoral adipose tissues expressed CYP19A1 approximately threefold higher than tumor itself (p = 0.001). A nonsignificant trend toward low expression of CYP17A1 was observed in peritumoral compared to tumor tissue (p = 0.687). Clinicopathological parameters and patient characteristics which are accepted as risk factors for breast cancer were also associated with individual and combined expressions of CYP17A1 and CYP19A1. This study offers that evaluation of CYP17A1 and CYP19A1 local expression levels might be useful for deciding on personalized treatment approaches and more accurate diagnosis, when evaluated together with several clinicopathological and disease risk factors. Considering the key role of these CYPs in estrogen synthesis, determining their expression levels may be useful as a postdiagnostic marker and for choosing the right treatment method in addition to the conventional approach.

Keywords: Aromatase; Breast cancer; CYP17A1; CYP19A1; Local estrogen synthesis.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aromatase / genetics*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Postmenopause
  • Precision Medicine
  • Prognosis
  • Steroid 17-alpha-Hydroxylase / genetics*

Substances

  • Aromatase
  • CYP19A1 protein, human
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase