Bmi-1 expression predicts prognosis in salivary adenoid cystic carcinoma and correlates with epithelial-mesenchymal transition-related factors

Ann Diagn Pathol. 2016 Jun;22:38-44. doi: 10.1016/j.anndiagpath.2015.10.015. Epub 2016 Mar 21.

Abstract

Salivary adenoid cystic carcinoma (AdCC) is known for its high propensity to invade and metastasize. Bmi-1 acts as an oncogene by controlling cell cycle and self-renewal of adult stem cells, and its overexpression correlates with metastasis and poor prognosis in several cancers. Epithelial-mesenchymal transition (EMT) plays a central role in cancer metastasis. A key step in EMT is the down-regulation of E-cadherin that can be repressed by the transcriptional factors, such as Snail and Slug. In the present study, we investigated Bmi-1, Snail, Slug, and E-cadherin expression by immunohistochemistry in 102 patients with AdCC and analyzed statistically whether their expression correlated with clinicopathologic factors and prognosis. Reverse transcription-polymerase chain reaction was also performed in 22 tumor tissues and the adjacent noncancerous tissues to confirm Bmi-1 status in AdCCs. Our data demonstrated significant associations between the tumor metastasis and the expression of Bmi-1, Snail, Slug, and E-cadherin. Furthermore, a high level of Bmi-1 was not only correlated with the overexpression of Snail and Slug but also indicated an unfavorable metastasis-free survival and served as a high-risk marker for AdCC. In addition, Bmi-1 messenger RNA level was found much higher in AdCC tissues than in the adjacent noncancerous salivary gland tissues. Our results suggest that Bmi-1 may play a crucial role in AdCC progression by interaction with EMT-related markers and predict poor survival.

Keywords: Bmi-1; EMT; Metastasis; Salivary adenoid cystic carcinoma.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Adenoid Cystic / diagnosis*
  • Carcinoma, Adenoid Cystic / metabolism*
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Middle Aged
  • Polycomb Repressive Complex 1 / metabolism*
  • Prognosis
  • Salivary Gland Neoplasms / diagnosis
  • Salivary Gland Neoplasms / metabolism*
  • Transcription Factors / metabolism

Substances

  • BMI1 protein, human
  • Biomarkers, Tumor
  • Transcription Factors
  • Polycomb Repressive Complex 1