[1169] Characterization and Comparison of Ovarian Primitive Neuroectodermal Tumors and Immature Teratomas by Immunohistochemistry and Fluorescence In-Situ Hybridization

Nancy M Joseph, Martin P Powers, Charles J Zaloudek. UCSF, San Francisco

Background: Ovarian primitive neuroectodermal tumors (oPNETs) are rare germ cell tumors thought to arise from the immature neuroepithelium (imNE) of teratomas. Limited studies have been performed to characterize the immunohistochemical profile of oPNETs or their presumed imNE precursors. Although oPNETs are thought to mimic central PNETs (cPNETs) rather than peripheral PNETs (pPNETs), it remains unknown whether oPNETs exhibit MYC amplification as seen in cPNETs or EWSRI translocation as seen in pPNETs. Deletion of PTEN was also tested as PTEN deletion is known to promote primordial germ cell proliferation.
Design: Immunostains for markers of germ cell tumors (Sox2, Sall4, Oct-4), cPNETs (CD56, nestin, Bcl2, chromogranin, synaptophysin), and pPNETs (Fli-1, CD99) were performed in 5 oPNETs and 11 immature teratomas. FISH analysis for nMYC, cMYC, EWSR1, and PTEN was performed in all 16 tumors.
Results: Immunostain results are summarized in the table below. No oPNETs (0/5) or imNE (0/11) showed amplification for nMYC or cMYC or an EWSR1 translocation. 20% of oPNETs (1/5) but no imNE (0/8) showed PTEN deletion.

 Diffuse/StrongFocalWeak/Negative
 imNEoPNETimNEoPNETimNEoPNET
CD5611/115/5    
Nestin10/104/4    
Chromo  1/112/510/113/5
Synapto1/11 3/112/57/113/5
Vimentin10/114/5  1/111/5
Sox210/115/51/11   
Sall47/112/52/11 2/113/5
Oct4  5/11 6/115/5
Pax811/115/5    
Bcl210/114/5 1/51/11 
P53 5/55/11 6/11 
CD99    1/15/5
Fli1    11/115/5



Conclusions: Overall, the immunostaining patterns within the imNE of teratomas were similar to those of oPNETs, with the exception of p53 which consistently showed more expression in oPNETs, and Oct4, which was focally expressed within imNE in 45% of cases, but not within the oPNETs. The increased p53 expression in oPNETs may indicate tumor progression. The focal Oct4 expression within immature teratomas appeared mainly in occult foci of embryonal carcinoma in these tumors. Both tumor types showed strong staining for CD56, nestin, vimentin, Sox2, Pax8, and Bcl2. Unlike pPNETs, imNE and oPNETs were negative for CD99 and only weakly positive for Fli1. Unlike cPNETs, expression of chromogranin and synaptophysin was negative to focal in both oPNETs and imNE. oPNETs expressed Sall4 (40% positive) and Sox2 (100% positive), which represent diagnostic pitfalls as these markers are commonly used to diagnose other germ cell tumors. FISH testing for nMYC and cMYC amplification and EWSR1 translocation was negative in all oPNETs and imNEs suggesting that the molecular mechanisms of oPNETs do not mimic either central or peripheral PNETs.
Category: Gynecologic & Obstetrics

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 202, Tuesday Morning

 

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