[1034] Reverse Phase Protein Lysate Array (RPPA) Identifies Differential Protein Expression in Uterine Carcinosarcoma.

Elizabeth D Euscher, Caimiao Wei, Broaddus R Russell. MD Anderson Cancer Center, Houston, TX

Background: Uterine carcinosarcoma (CS) is a highly aggressive tumor characterized by admixtures of carcinoma (CA) and sarcoma (SA). Although the biphasic pattern of CS is diagnostic, individual tumors have marked heterogeneity with respect to differentiation. We adapted RPPA to the use of formalin-fixed, paraffin embedded sections of uterine CS to determine if differential patterns of protein expression correlate with histologic features of CS.
Design: We evaluated 52 uterine CS for histologic subtype of CA, presence/histologic subtype of heterologous elements (HE), ratio of CA to SA, depth of myoinvasion (MI), presence of CA or SA in MI, lymphovascular invasion, presence/histology of lymph node metastases, and presence/histology of recurrences. 50 µg of tumor protein were extracted from each block, and these proteins were subjected to RPPA analysis using a panel of 120 different antibodies previously validated for this assay.
Results: CS with HE showed the most prominent differences in protein expression. Twenty-eight proteins were differentially expressed in CS with chondrosarcoma (ChS) or rhabdomyosarcoma (RS) compared to CS without RS or ChS. These findings are summarized in tables 1 and 2.

Proteins Differentially Expressed in CS with Rhabdomyosarcoma¹
Proteinp Value
A_RAF0.01
Caveolin0.01
CHK10.02
ATM0.01
Cyclin D1<0.01
EGFR.V0.01
ER<0.01
JUNB0.03
p530.03
PAX2<0.01
SRC0.02
STAT30.01
HER2/neu0.03
VEGFR<0.01
¹proteins uniformly upregulated



Proteins Differentially Expressed in CS with Chondrosarcoma¹
Proteinp Value
X4EBP10.02
AKT.V0.03
BIM.V0.01
Casein kinase0.03
CHK20.03
KU800.02
PLK10.02
YBI_pS1020.02
Cyclin E10.01
FAK_pY9250.02
GSK3a0.03
IRS1.V0.02
NFKB_p650.03
SRC0.02
¹proteins uniformly downregulated


Conclusions: The presence of HE in CS confers a worse prognosis. Using a novel technology, we have identified a number of different proteins that may be responsible for the more aggressive clinical behavior of CS with HE. Pertinent to therapy, some of the identified upregulated proteins (EGFR, ER, Her2, BEGFR2, AKT and SRC) are cell signalling pathway components that are potential therapeutic targets. These findings underscore the need for pathologists to recognize the presence of HE in CS.
Category: Gynecologic & Obstetrics

Wednesday, March 2, 2011 1:00 PM

Poster Session VI # 180, Wednesday Afternoon

 

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