1. Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India.
2. Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Rockville, Maryland, USA.
3. Urology Service, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
4. Bangalore Institute of Oncology - HCG, Bangalore, India.
5. Department of Genitourinary Pathology, Joint Pathology Center, Silver Spring, Maryland, USA.
Introduction and Objective: ERG oncogene fusions (predominantly TMPRSS2-ERG) represent the most common (50-70% frequency) and validated prostate cancer (CaP) genome alteration in the Western countries. A common TMPRSS2-ERG fusion type leads to the androgen dependent tumor cell specific expression of the TMPRSS2-ERG fusion transcript and amino terminally truncated ERG oncoprotein. CaP prevalence and aggressiveness, as well as genomic alterations vary in different geographic locations in the world. Recent studies from our group highlighted significantly lower frequency of ERG alterations in prostate index tumors of African American men (~30%) in comparison to Caucasian Americans (~60%). Further, much lower frequencies (10 -25%) of ERG alterations have been reported in studies from China and Japan. There is no study on ERG alterations in CaP patients from India, representing a significant portion of the world male population. This study focuses on the frequency of ERG oncoprotein expression in CaP patients from India.
Methods: De-identified formalin-fixed paraffin-embedded (FFPE) specimens from radical prostatectomy (RP) specimens of 51 patients from the Rajiv Gandhi Cancer Institute and Research Centre (RGCI), New Delhi, India, were analyzed for ERG alterations. The ERG oncoprotein expression as a surrogate of ERG gene fusions was analyzed by using a highly specific ERG monoclonal antibody (9FY). TMPRSS2-ERG fusion was assessed by fluorescent in situ hybridization (FISH) assays using the break-apart ERG probes.
Results: Specimens reflecting prior hormonal treatment, or lacking any tumor content, were excluded from the analyses. Of the thirty evaluable specimens, ERG positive tumors were present in 8 cases (27%) and one tumor specimen exhibited rare ERG positive cells. None of the benign glands were positive for ERG supporting previous studies showing complete specificity of the ERG oncoprotein for detection of tumors cells in prostate.
Conclusions: Frequency of ERG oncoprotein expression is much lower in CaP patients from India in comparison to higher frequency of ERG alterations noted in Western countries. ERG frequency in Indian CaP is similar to observations from Japan and China. Since ERG oncogenic activation is a promising biomarker and therapeutic target for CaP, careful evaluation of ERG is needed in CaP patients from different parts of the world.
Keywords: prostate cancer, ERG oncogene, India.