Analysis of Mel-18 expression in prostate cancer tissues and correlation with clinicopathologic features

Urol Oncol. 2011 May-Jun;29(3):244-51. doi: 10.1016/j.urolonc.2009.02.004. Epub 2009 Apr 22.

Abstract

Objective: Mel-18 is a member of the polycomb group (PcG) of proteins, which are chromatin regulatory factors that play an important role in development and oncogenesis. This study was designed to investigate the clinical and prognostic significance of Mel-18 in the patients with prostate cancer.

Patients and methods: Immunostaining with Mel-18 specific antibodies was performed on paraffin sections from 202 patients. Correlations between Mel-18 and the Gleason grading system, clinical stage, serum prostate-specific antigen (PSA) levels, and age were evaluated. PSA recurrence in 76 patients who underwent radical prostatectomy and survival in 59 patients with metastases at diagnosis were analyzed to evaluate the influence of Mel-18 expression in cancer progression using Kaplan-Meier analysis and multivariate Cox regression analysis.

Results: Staining was seen in all prostatic tissues. Mel-18 expression was significantly reduced in the prostate cancer patients with PSA levels over 100 ng/ml (P=0.009), advanced clinical stage (>T4, N1, or M1 disease, P=0.029), higher Gleason grade or with a higher Gleason score (P=0.018) than in those with other clinicopathologic features. Negative expression of Mel-18 was associated with significantly higher rates of PSA recurrence after radical prostatectomy than with positive expression of Mel-18 (P = 0.029), and was an independent predictor of PSA recurrence (P=0.034, HR=2.143) in multivariate analysis. Similarly, metastatic prostate cancer patients with negative expression of Mel-18 showed significantly worse survival compared with the positive expression of Mel-18 (P=0.025). In multivariate analysis, negative expression of Mel-18 was an independent predictor of cancer-specific survival (P=0.024, HR=2.365).

Conclusion: Our study provides important evidence for the recognition of Mel-18 as a tumor suppressor. The expression of Mel-18 showed potential as a prognostic marker for human prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / secondary
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Polycomb Repressive Complex 1
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Prostatectomy
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / genetics
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate

Substances

  • BMI1 protein, human
  • MYC protein, human
  • Nuclear Proteins
  • PCGF2 protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Repressor Proteins
  • Polycomb Repressive Complex 1