[50] Expression of Mesenchymal Developmental Antigens in Chordoma

Selene Koo, Anthony G Montag. University of Chicago, Chicago, IL

Background: Chordomas are thought to derive from notochordal remnants. The transcription factor brachyury is a specific marker for chordomas that is expressed in all stages of notochord formation, but expression of other developmental antigens has not been broadly studied in chordomas. This study explores the expression in chordomas of proteins important for embryonal notochord and somite development and compares it with expression in other myxoid tumors.
Design: With IRB approval, cases were retrieved from the paraffin archive, and a tissue microarray was prepared with duplicate cores from 20 chordoma cases from 12 patients, 7 cases of intramuscular myxoma, and 3 cases of extraskeletal myxoid chondrosarcoma (EMC). Immunohistochemical stains were performed for beta-catenin, Bmp2, fibronectin, Foxa2, Noggin, Notch-1, Noto, Pax8, quaking, and Sox9, and reactivity scored as positive (>10%) or weak to negative (≤10%). When discrepancies in reactivity occurred between paired cores, the higher value was used.
Results: Staining results are summarized in the table below.

AntigenChordomaIntramuscular myxomaEMC
Bmp219/194/72/2
Notch-119/197/73/3
Sox918/183/72/3
Noggin17/197/73/3
Quaking17/197/73/3
Fibronectin15/190/70/3
Beta-catenin13/180/70/2
Noto7/190/72/2
Foxa25/197/71/2
Pax83/180/71/2


Over 75% of chordomas expressed fibronectin and quaking, similar to the profile of late notochord development. Other proteins important for notochord and somite development were expressed to varying degrees in all tumor types tested. Beta-catenin expression in chordoma cases differed by grade; low grade conventional tumors showed distinct membranous staining, which was absent in high grade chordomas (p=0.002). Differential staining for chordomas vs. intramuscular myxomas and EMC was identified for fibronectin (p=0.0005 vs. myxomas, p=0.02 vs. EMC). Bmp2, Sox9, beta-catenin, and Foxa2 were expressed in a significantly higher percentage of chordomas compared to myxomas (p=0.01, 0.003, 0.002, and 0.001, respectively), but not compared to EMC (p=1, 0.14, 0.11, and 0.5, respectively).
Conclusions: The expression of developmentally related mesenchymal antigens in chordomas is consistent with their origin from notochord remnants, and their expression of fibronectin and quaking is similar to cells in the later stages of notochord differentiation. Loss of beta-catenin staining correlates with transformation to high grade or de-differentiated phenotype in chordoma. Other developmental antigens are much more commonly expressed in chordoma than in other myxoid tumors.
Category: Bone & Soft Tissue

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 9, Tuesday Afternoon

 

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