title: Nuclear C-MYC expression level is associated with disease progression and potentially predictive of two year overall survival in prostate cancer.
abstract: OBJECTIVE
  Upregulation of nuclear C-MYC protein has been reported to be an early event in prostate cancer (PCa); however, its clinicopathological and prognostic significance remain controversial. We determined the association of nuclear C-MYC protein expression with clinicopathological parameters, prognosis, ETS-related gene (ERG) expression, and TMPRSS2-ERG status in PCa.
  
  
  METHODS
  Nuclear C-MYC and ERG expression by immunohistochemistry and TMPRSS2-ERG status by triple-color probe fluorescence in situ hybridization assay were determined in 50 hormone-naïve PCa patients and 31 radical prostatectomy specimens.
  
  
  RESULTS
  Nuclear C-MYC immunostaining was negative, positive, and strong positive in 27.5%, 32.5%, and 40.0% of cases, respectively. C-MYC immunostaining was significantly associated with clinical T stage (P < 0.001), distant metastasis at the time of diagnosis (P < 0.001) and TMPRSS2-ERG status (P = 0.001) but not with ERG immunostaining (P = 0.818). In the Kaplan-Meier analysis, C-MYC positive cases were found to have worse 2-year OS compared with C-MYC negative cases (P = 0.027). However, in the univariate Cox analysis, only TMPRSS2-ERG status (hazard ratio [HR] 0.189, 95% CI 0.057-0.629; P = 0.007) and distant metastasis (HR 3.545, 95% CI 1.056-11.894; P = 0.040) were significantly associated with 2-year OS. After adjusting for these two factors, TMPRSS2-ERG status still impacted 2-year OS (HR 0.196, 95% CI 0.049-0.778; P = 0.020).
  
  
  CONCLUSIONS
  Nuclear C-MYC overexpression may be associated with disease progression and potentially predictive of 2-year OS in PCa. This is the first study to demonstrate an association between nuclear C-MYC immunostaining and TMPRSS2-ERG status in PCa.
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Hanying
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Fankai
authors.initials: F
authors.lastname: Meng
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Zeming
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002467:Cell Nucleus / Q000737:chemistry* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics; D000071230:Transcriptional Regulator ERG
chemical_list: D014408:Biomarkers, Tumor; C072312:ERG protein, human; C489427:MYC protein, human; D015514:Oncogene Proteins, Fusion; D016271:Proto-Oncogene Proteins c-myc; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
keywords: C-MYC; ERG; TMPRSS2-ERG; immunohistochemistry; prostate cancer