title: Weaker ERG expression in patients with ERG-positive prostate cancer is associated with advanced disease and weaker androgen receptor expression: An Indian outlook.
abstract: BACKGROUND
  Gene fusion between TMPRSS2 and ERG has a causal role in prostate cancer initiation. However, studies evaluating its role clinically have shown conflicting results. We investigated simultaneously multiple aspects of ERG, namely, "presence" and "strength" of ERG expression and "correlation" of ERG with other common clinicopathological parameters.
  
  
  METHODS
  From January 2012 to November 2013, the status of ERG, androgen receptor (AR), and p53 was prospectively determined by immunohistochemistry unselectively in all types of specimens positive for prostate cancer. "Strength" of expression was measured in terms of "intensity" as well as "percentage positivity," with each parameter given a score from 0 to 3 based on fixed protocol, which was tested for interrater variability as well as test-retest reliability. Data were collected for age, Gleason score, prostate specific antigen levels, presence of perineural invasion and lymphovascular invasion, high-grade prostatic intraepithelial neoplasia, and cancer stage.
  
  
  RESULTS
  In total, 100 specimens were analyzed, and overall 51 patients had ERG-positive immunostaining. ERG-positive tumors had lower presence of high-grade prostatic intraepithelial neoplasia and p53 positivity, with no significant difference in prostate specific antigen levels, Gleason scores, and presence of lymphovascular invasion. Moreover, 54 patients had complete stage information, and the absolute number of patients with ERG positivity increased with increasing clinical stage. Among these, 30 patients were ERG positive, and ERG score had strong positive correlation with AR expression (Spearman correlation coefficient 0.677). However, median ERG scores showed a significant decline (consistent across percentage positivity and intensity) in patients with stage 4 disease, and score ≤ 2 had 88.2% specificity in identifying patient with stage 4 disease. Cohen׳s κ = 0.81, whereas intraclass correlation coefficient was 0.95, indicating substantial agreement and near-perfect reproducibility of scoring scheme for immunohistochemistry.
  
  
  CONCLUSIONS
  ERG-positive tumors increase in proportion with increasing stage of disease, but strength of ERG expression in ERG-positive patients shows a significant decline, or "loss," in patients with stage 4 disease. This may have potential therapeutic implications as ERG expression score showed strong positive correlation with AR expression score.
authors.affiliation: Department of Pathology, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, India. Electronic address: moushumisuryavanshi@gmail.com.
authors.forename: Moushumi
authors.initials: M
authors.lastname: Suryavanshi
authors.affiliation: Department of Pathology, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, India.
authors.forename: Anurag
authors.initials: A
authors.lastname: Mehta
authors.affiliation: Department of Urology, Sri Sathya Sai Institute of Higher Medical Sciences, Prashantigram, Andhra Pradesh, India.
authors.forename: Jiten
authors.initials: J
authors.lastname: Jaipuria
authors.affiliation: Department of Urooncology, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, India.
authors.forename: Ashwani Kumar
authors.initials: AK
authors.lastname: Sharma
authors.affiliation: Department of Urooncology, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, India.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Rawal
authors.affiliation: Department of Pathology, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Seth
mesh_terms: D000368:Aged; D006801:Humans; D007124:Immunoenzyme Techniques; D007194:India; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D000071230:Transcriptional Regulator ERG; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C072312:ERG protein, human; D011944:Receptors, Androgen; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D016159:Tumor Suppressor Protein p53; D017430:Prostate-Specific Antigen
keywords: AR; ERG; IHC; Prognosis; Prostate cancer