Expression of cell cycle regulatory proteins in eyelid sebaceous gland carcinoma: low p27 expression predicts poor prognosis

Exp Eye Res. 2014 Jan:118:46-52. doi: 10.1016/j.exer.2013.10.022. Epub 2013 Nov 8.

Abstract

Prognosis of eyelid sebaceous gland carcinoma is largely unpredictable and there are few practically available markers for predicting patients' prognosis. Dysregulation of cell cycle progression is strongly associated with the development of cancer and the cancer prognosis. We investigated the expression of cell cycle regulatory proteins in eyelid sebaceous gland carcinoma and estimate their value as prognostic predictors. Forty-three cases of eyelid sebaceous gland carcinoma were included in this study. Immunohistochemistry for the p53, p21, p27, cyclin E, p16, cyclin D1, and phosphorylated Rb (pRb) proteins was performed using archival paraffin blocks. Correlations between clinical features and protein expression were evaluated statistically. Nine patients showed lymph node or distant metastasis, and the remaining patients showed localized disease. High expression of p21, p27, cyclin E, and p16 was found in the majority of tumor cell nuclei, whereas these proteins were rarely expressed in the normal sebaceous glands. However, pRb was focally lost in a subset of cases. Patients showing diffuse p27 expression developed metastasis less commonly than those with negative or focal p27 expression (log-rank test, p = 0.008). Aberrant expression of cell cycle regulatory proteins was observed in eyelid sebaceous gland carcinoma, suggesting that cell cycle dysregulation is involved in the pathogenesis of this tumor. Decreased p27 expression is a predictive biomarker of an unfavorable prognosis of eyelid sebaceous gland carcinoma.

Keywords: cell cycle; p27; prognosis; sebaceous gland carcinoma.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Cycle
  • Cyclin-Dependent Kinase Inhibitor p27 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics*
  • DNA, Neoplasm / genetics*
  • Eyelid Neoplasms / genetics*
  • Eyelid Neoplasms / metabolism
  • Eyelid Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Sebaceous Gland Neoplasms / genetics*
  • Sebaceous Gland Neoplasms / metabolism
  • Sebaceous Gland Neoplasms / pathology

Substances

  • DNA, Neoplasm
  • Cyclin-Dependent Kinase Inhibitor p27