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Introduction: Biochemical markers, such as AMACR and p63 have improved diagnostic precision of prostate cancer. Recently, recurrent TMPRSS2-ERG genomic fusion has been demonstrated in half of prostate cancers. We have developed a monoclonal anti-ERG antibody that demonstrated 99.9% specificity in detecting the protein product of recurrent ERG fusions. Previously we have shown that when AMACR and ERG mRNA expression were examined together, 96.4% of cases were positive for at least one of the two markers. We reasoned that by combining ERG with AMACR immunohistochemical staining, diagnostic sensitivity and specificity can be improved in prostate biopsy specimens.
Materials & Methods: In a retrospective set of 88 patients undergoing prostate biopsies, prostate cancer was identified in 44 patients. Ten of these patients subsequently underwent radical prostatectomy. We evaluated 385 slides from the 88 biopsy sets by IHC with 350 stained for ERG only and 35 stained for both ERG and AMACR.
Results: AMACR was detected in 28 of 31 (90.3%) and ERG in 37 of 70 (52.8%) of tumor positive biopsies evaluated. Of the three biopsies with benign tissue only, one had AMACR positive glands. However, in six other biopsies, both neoplastic and benign glands were positive for AMACR. ERG positivity in benign glands was detected in only 1/280 (0.4%) of biopsies (specificity >99%). Of the three slides with AMACR negative tumors, two were positive for ERG.
Conclusions: Our findings highlight that detection of ERG oncoprotein when combined with AMACR has potential to improve diagnostic sensitivity and specificity in prostate biopsy specimens.