PATHOLOGY

Are There Morphologic Correlates of Prostate Cancer Associated with TMPRSS2-ERG Molecular Abnormalities?
SW Fine, A Gopalan, M Leversha, SK Tickoo, HA Al-Ahmadie, S Olgac, W Gerald, VE Reuter
Memorial Sloan Kettering Cancer Center, New York, NY, USA
Mod Pathol. 2007; 20 (suppl 2): 146A

• Background: Recent studies have shown that TMPRSS2-ERG fusion is common in prostate cancer, varying from 30-70% of cases in published series. The molecular abnormalities include formation of a fusion gene, in a majority of cases due to deletion of a region on chromosome 21. While the histologic features of these tumors have not been elucidated, it has been suggested that these molecular genetic events may be associated with distinct morphologic characteristics, such as cribriform architecture and the presence of blue mucin.
• Design: Blinded histologic review was conducted on 67 cases comprising two tissue microarrays (TMA) on which fluorescent in situ hybridization (FISH) had previously been performed to delineate molecular abnormalities.
• Results: By FISH, 37/67 cases showed molecular abnormalities, including 21 deletions, 5 translocations, and 11 cases with other abnormalities. The other 30 cases were negative on FISH analysis. 8/37 (16.7%) cases with and 9/30 (30%) cases without molecular abnormalities showed cribriform glands or glomerulations. Intraluminal blue mucin was present in 15/37 (40.5%) cases with and 11/30 (36.7%) cases without genetic events. Overall, 19/30 (63.3%) cases without FISH abnormalities showed no specific morphologic features. Cribriform glands/glomerulations were present in 8/17 cases with molecular changes and 9/17 FISH negative cases.
• Conclusions: In this analysis, we observe that TMPRSS2-ERG-related abnormalities do not correlate with specific tumor histology. Similarly, cribriform architecture is seen equally in cases with and without these genetic events. These findings suggest a lack of association between FISH-detected molecular changes and these morphologic findings. Further studies in larger cohorts of tissue are in progress to confirm these observations.
  
  
• Editorial Comment
  The paper by Fine SW et al. from the Memorial Hospital (New York) is at odds with the paper by Mosquera MJ et al. from the Brigham and Women’s Hospital (Boston). Fine SW et al. observed that TMPRSS2-ERG abnormalities did not correlate with any specific or peculiar feature of prostate adenocarcinoma. One of the reasons for the discrepancy between the two papers may be related to the sophisticated techniques used in cancer molecular cytogenetic analysis.
  So far, the TMPRSS2-ERG fusion is detected by molecular cytogenetic analysis available only in research laboratories. Future efforts will be directed at characterizing the expressed protein products of this gene fusion which may be detected by immunohistochemistry. This latter technique is available to all routine laboratories of pathology.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil