[69] SMAD Signaling in Liposarcomas.

Jennifer E Pogoriler, Anthony G Montag. University of Chicago Medical Center, IL

Background: Signaling by members of the TGFβ superfamily affects development of normal adipocytes. TGFβ is thought to negatively regulate adipogenesis, while BMPs generally positively contribute to adipocyte development. Among other intermediates, both BMPs and TGFβ receptors transduce signals by phosphorylating SMAD family members, allowing them to regulate transcription of target genes, including PPARγ, a key regulator of adipogenesis. We hypothesized that SMAD signaling would be different among the different subtypes of liposarcomas.
Design: We constructed a liposarcoma tissue microarray that included well-differentiated (WD), de-differentiated (DD), myxoid, round-cell and pleomorphic liposarcomas, including several samples with both low and high grade components. We used immunohistochemistry to assess expression and localization of SMAD4, SMAD2/3, PPARγ, c-jun and ask-1. Staining was scored as 0 (none), 1 (<5%), 2 (5 to 50%), or 3 (greater than 50%). For analysis purposes, scores 2 and 3 were considered positive staining.
Results: We found that nuclear SMAD4 was present in 7 of 10 DD liposarcomas but was negative in all WD liposarcomas, including the well-differentiated component of DD tumors. SMAD4 was positive in almost all myxoid, round cell, and pleomorphic liposarcomas. In contrast, nuclear SMAD2/3 was only detected in one DD tumor and was entirely absent from WD tumors. It was detected in 10/16 myxoid, 8/8 round cell and 11/12 pleomorphic liposarcomas. Within each tumor subtype there was no relationship between SMAD2/3 or SMAD4 expression and PPARγ, c-jun and ask-1 expression.

Liposarcoma immunohistochemistry
 SMAD4SMAD2/3c-JunAsk-1PPAR
pure WD0/100/101/101/100/10
WD component0/120/121/121/122/12
DD7/100/107/108/108/10
pure myxoid9/105/105/101/104/10
myxoid component6/65/60/60/64/6
Round cell8/88/82/83/86/8
Pleomorphic11/1211/128/1210/128/12



Conclusions: The nuclear localization of SMAD4 and SMAD2/3 in myxoid/round cell and pleomorphic liposarcomas suggests that signaling through a TGFβ receptor family member is occurring. Although SMAD2/3 was negative in DD liposarcomas, the common mediator SMAD4 was positive, suggesting that signaling through BMP or TGFβ receptors is occurring, perhaps through a different receptor-activated SMAD family member.
Category: Bone & Soft Tissue

Monday, February 28, 2011 1:00 PM

Poster Session II # 24, Monday Afternoon

 

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