[1000] Comparison of Immunohistochemical Profile of Prostate Cancer Tumorgrafts and Their Donor Tumor

V Tzelepi, S Maity, J Yang, E Efstathiou, A Aparicio, C Logothetis, P Troncoso, N Navone. M.D. Anderson Cancer Center, Houston

Background: The study of prostatic cancer (PCa) is limited by the lack of models that reflect its complexity. Tumorgrafts (TGs) intent was to bridge the gap between existing models and human PCa. We compare the immunohistochemical profile of five new TGs and their donor tumors (DT) in order to determine whether this profile will inform on the optimum use of TGs.
Design: Samples from primary (TG1,4,5) and metastatic (TG2,3) PCa specimens were implanted subcutaneously in SCID mice. A tissue microarray was constructed containing cores from different passages. The TGs were compared to their DT in terms of histology and immunohistochemical expression of basic markers [AR, PSA, AE1/AE3, chromogranin (ChrA), synaptophysin (syn), ki67]. In order to test the presence of concordance in signaling pathways, expression of components of pathways implicated in PCa progression (PTEN, pAKT, bcl2, CD31, p53) was assessed in TG4 and its DT.
Results: Five TGs and 10 sublines were developed: TG1,2: Adenocarcinoma with neuroendocrine (NE) differentiation (positive for AR, PSA, AE1/AE3 and syn, ki67=10%) TG3A,3B,3C,5A: Adenocarcinoma (positive for AR, PSA and AE1/AE3, ki67<10%) TG4A,4B,4C: Large cell NE Carcinoma (LCNEC) (positive for AE1/AE3, syn and ChrA, ki67=95%) TG4D,4E,4F,5B,5C,5D: Small Cell Carcinoma (SCC) (positive for syn and ChrA, dot-like expression of AE1/AE3, ki67=95%). The histology and the expression of basic markers of the TGs matched their DT. Additionally, proliferation rate, p53 expression and vascularity seem to be in concordance. However, bcl2 was downregulated and p-AKT was upregulated in some TGs compared to the DT.

Expression profile of TG4 and its DT
p53PTEN*pAKT*bcl2*ki67*CD31**
DT (mixed)Adenocarcinoma+2020303013
SCC+080609521
LCNEC+0201009510
TG4DSCC+109109518
TG4ESCC+189295
TG4FSCC+172095
TG4ALCNEC+1193499512
TG4BLCNEC+81007295
TG4CLCNEC+4100195
*%positive cells-mean, ** /high power field


Conclusions: Our data show that TGs do not share all signaling pathways with their DT. These data support the hypothesis that the optimum use of TGs will require understanding of their molecular features. Furthermore, they suggest that a panel of TGs will be needed to model the complexity of PCa. Future studies will determine the effect of the murine background on TG expression profile in order to gain insight into PCa progression and survival pathways.
Category: Genitourinary (including renal tumors)

Wednesday, March 24, 2010 1:00 PM

Poster Session VI # 112, Wednesday Afternoon

 

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