title: Immunohistochemical expression of Ets-related gene-transcriptional factor in adenocarcinoma prostate and its correlation with Gleason score.
abstract: BACKGROUND
  Prostate carcinoma is the second leading cause of cancer-related deaths in males worldwide. The burden is expected to grow 1.7 million new cases and 499,000 new deaths by 2030. In developing countries such as India, prostate carcinoma will show an increase by 140% in the next few years. Although the diagnosis of prostate carcinoma can usually be made on histological features, now a days many immunohistochemical (IHC) markers are used to distinguish it from benign mimickers as well as in predicting prognosis and treatment. Out of these markers, Ets-related gene (ERG product) is a proto-oncogene which participates in chromosomal translocations and is frequently over expressed in prostate carcinoma which harbors ERG-transmembrane protease, serine 2 fusion.
  
  
  METHODS
  Fifty cases of carcinoma prostate diagnosed in needle biopsies and prostatic chips, in the Department of Pathology of a tertiary care teaching hospital in Punjab, India, were included in the present study. The slides were observed under the light microscope, and Gleason scoring was done using the 2005 International Society of Urological Pathology modified Gleason system. IHC study for ERG expression was done on all the cases, for which anti-ERG monoclonal rabbit clone antibody EP111 (Dako, Denmark) was used. Lymphocytes and endothelial cells were taken as in built positive controls for staining. The intensity of ERG positivity was scored as no staining (0), weak staining (+1), moderate staining (+2) and intense staining (+3). The H score was then calculated by multiplying the intensity of the stain with the percentage (0-100) of the cells showing that staining intensity. The H-score has a range of 0-300. The relationship between IHC expression and clinico-pathological parameters was compared and analyzed using Chi-square test. P < 0.05 was considered statistically significant.
  
  
  RESULTS
  Majority of patients included in the study were in the age group of 61-80 (84% of the total). When ERG expression was studied with age-specific rates, it was not found to be statistically significant. The most common pattern noted in the present study was 4 + 3, constituting 36% of total, followed by 3 + 4 constituting 32%. Calculating the score, the majority of patients had a Gleason score of 5-8, constituting 76% of total. Out of the total fifty cases of prostate carcinoma, ERG was positive in 29 cases (58%) and negative in 21 cases (42%). Fourteen out of 21 (48%) of the ERG positive cases had an intensity score of 3. When the ERG intensity was correlated with the Gleason score group, it was seen that patients having Gleason score 7-8 showed ERG positivity in 19 out of 38 cases (50%), with 11/19 (57%) cases showing an ERG intensity score of 3. The Gleason score group 9-10 showed ERG positivity in 83% (10/12) cases, 20% (2/10) cases showing intensity score of 3. This correlation was found to be statistically significant.
  
  
  CONCLUSIONS
  ERG immunostaining was performed in a small Indian cohort of prostate cancer patients, diagnosed in trucut biopsy specimens and prostatic chips. ERG expression was found in 58% patients. An increase in the ERG expression was observed with an increase in Gleason score. The intensity of ERG expression, however, decreased with an increasing Gleason score.
authors.affiliation: Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Mannan
authors.affiliation: Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.
authors.forename: Tejinder Singh
authors.initials: TS
authors.lastname: Bhasin
authors.affiliation: Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.
authors.forename: Mridu
authors.initials: M
authors.lastname: Manjari
authors.affiliation: Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.
authors.forename: Gagandeep
authors.initials: G
authors.lastname: Singh
authors.affiliation: Department of Pathology, Gian Sagar Medical College and Hospital, Patiala, Punjab, India.
authors.forename: Puneet Kaur
authors.initials: PK
authors.lastname: Bhatia
authors.affiliation: Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.
authors.forename: Sonam
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D007194:India; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D060787:Neoplasm Grading; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D000090063:Proto-Oncogene Mas; D000071230:Transcriptional Regulator ERG / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C072312:ERG protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D000071230:Transcriptional Regulator ERG