γ-glutamyl-hydrolase (GGH) is a ubiquitously-expressed enzyme that regulates intracellular folate metabolism for cell proliferation, DNA synthesis, and repair. Employing GGH immunohistochemistry on a tissue microarray with 12,427 prostate cancers, we found that GGH expression was negative to low in normal prostate epithelium, whereas 88.3% of our 10,562 interpretable cancers showed GGH expression. GGH staining was considered as low intensity in 49.6% and as high intensity in 38.6% of cancers. High GGH expression was linked to the TMPRSS2:ERG-fusion positive subset of cancers (p < 0.0001), advanced pathological tumor stage, and high Gleason grade (p < 0.0001 each). Further analysis revealed that these associations were merely driven by the subset of ERG-negative cancers, High GGH expression was weakly linked to early biochemical recurrence in ERG negative cancers (p < 0.0001) and independent from established histo-pathological parameters. Moreover, GGH expression was linked to features of genetic instability, including presence of recurrent deletions at 3p, 5q, 6q, and 10q (PTEN, p ≤ 0.01 each), as well as to accelerated cell proliferation as measured by Ki67 immunohistochemistry (p < 0.0001). In conclusion, the results of our study identify GGH as an ERG subtype specific molecular marker with modest prognostic relevance, which may have clinical relevance if analyzed in combination with other molecular markers.

Background: Gliomas are the most relevant primary brain tumors. Diffuse astrocytomas are the most common type of gliomas .The distinction of diffuse infiltrating astrocytoma from reactive astrocytosis is one of the most difficult differential diagnosis especially with small biopsies (e.g. stereotactic biopsies). Several markers were used for this differentiation such as glial fibrillary acidic protein, ki67 and p53; but each of them has problems with sensitivity and specificity. The immunohistochemical markers such as mutant isocitrate dehydrogenase 1 (IDH1), EGFR and Bcl2 may be useful in this differentiation. Aim: This study was conducted to clarify the value of IDH1, EGFR and Bcl2 protein expression in making a clear distinction between diffuse infiltrating astrocytomas and morphologically similar reactive astrocytosis. Methods: Fifty representative cases; 30 cases WHO grade II diffuse astrocytomas and 20 cases of reactive conditions were examined immunohistochemically using antibodies against mutant IDH1, EGFR and Bcl2. Results: IDH1 was positive in 60% of astrocytomas cases but it was totally absent in reactive astrocytosis. EGFR was expressed in 50% of astrocytomas; but it was not expressed in reactive astrocytosis. Bcl2 expression was detected in 56.7% of astrocytomas cases. However; it was expressed also in 75% of reactive astrocytosis cases. Conclusion: IDH1, EGFR were the most useful IHC markers in the discrimination of low grade diffuse astrocytomas WHO II from reactive astrocytosis; particularly in small biopsies. Bcl2 play no role in this differentiation