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


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).


CONCLUSIONS
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.
Wang
Wei
W
Department of Urology, Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Lin
Tianxin
T
Huang
Jian
J
Hu
Weilie
W
Xu
Kewei
K
Liu
Jun
J
D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
C069077:BMI1 protein, human; C489427:MYC protein, human; D009687:Nuclear Proteins; C489348:PCGF2 protein, human; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1