The Utility of ERG Immunohistochemistry in Converting “Suspicious for” to “Definite” Lymphovascular Invasion in Non-Seminomatous Germ Cell Tumor of Testis
Hongying Huang, Sana Jadallah, Ying-bei Chen, Anuradha Gopalan, Hikmat A Al-Ahmadie, Samson W Fine, Victor E Reuter, Satish K Tickoo. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Identifying lymphovascular invasion (LVI) is crucial to the management of clinical stage I non-seminomatous germ cell tumors (NSGCT) because of its role in predicting disease relapse. Histologically unequivocal LVI is characterized by aggregates of tumor cells attached to the identifiable endothelial lining, projecting into vascular lumina. However, when vessels are entirely occluded by tumor, without endothelial lining being obvious, morphology alone is insufficient for definitive diagnosis of LVI. The differential diagnosis in such instances includes satellite tumor deposits or tubules filled by tumor cells. Therefore, there is a need to identify good vascular marker(s) to address this issue. ERG, an ETS family transcription factor, is known to be expressed in endothelial nuclei of both blood vessels and lymphatics. In this study, we investigated the utility of ERG immunohistochemistry (IHC) in identifying LVI in testicular NSGCTs, focusing on cases where there was a suspicion of LVI on H&E evaluation.
Design: ERG and CD31 IHC was performed in FFPE tissue sections from 30 orchiectomy specimens of NSGCT, including 15 cases with histologically unequivocal LVI and 15 in which LVI was suspected. Histologically suspicious LVI consisted of tumor cells entirely filling and plugging tubular structures outside of the confines of the main tumor. The utility of each marker in identifying LVI was evaluated independently and the results were compared.
Results: In all cases tumor cells occupying the unequivocal or suspected vascular spaces were of embryonal carcinoma. In all 15 cases suspected for LVI, the suspicious vascular spaces were also associated with inflammation and reactive stromal changes. In 14/15 (93%) cases suspicious for LVI, ERG clearly highlighted endothelial nuclei of the tumor-plugged vessels. Of these 14, 5 cases showed convincing CD31 expression in these vessels, whereas CD31 expression was very faint, equivocal in the other 9. On the contrary, histologically unequivocal vascular invasion was highlighted by both ERG (nuclear) and CD31 (cytoplasmic) immunoreactivity in all 15 cases.
Conclusions: Our data demonstrates that ERG immunohistochemistry is very helpful in identifying definitive LVI when it is difficult to be determined with certainty on H&E evaluation. ERG IHC is superior to CD31 in confirming LVI in suspicious foci. Whether this increased detection correlates with increased ability to predict disease relapse in non-seminomatous germ cell tumors remains to be determined.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 155, Wednesday Morning