The role of noncartilage-specific molecules in differentiation of cartilaginous tumors: lessons from chondroblastoma and chondromyxoid fibroma.
BACKGROUND
Chondroblastoma (CB) and chondromyxoid fibroma (CMF) are benign tumors of bone morphologically recapitulating cartilage differentiation. CMF can resemble high-grade central chondrosarcoma (HGCCS) because of its cellular atypia. The mechanism that drives this morphologic spectrum of cartilage differentiation is unclear.


METHODS
CMFs and CBs were hybridized on a complementary DNA microarray that was enriched for cartilage-specific genes. Data were analyzed by Linear Model for Microarray Analysis and were compared with previous data on osteochondromas and HGCCS. Verification was performed in an extended series.


RESULTS
None of the 68 genes that were differentially expressed in CB versus CMF, including several extracellular matrix (ECM) and ECM-degradation genes, were related specifically to cartilage. Perlecan, versican, collagen 4A2 (Col4A2), and cell-cell adhesion genes, such as CD166, were significantly higher in CMF. Sixty genes were expressed differentially in CMF versus HGCCS. Higher expression levels of CD166, cyclin D1 (CCND1), and p16INK4A were observed in CMF.


CONCLUSIONS
The current findings indicated that differential expression of adhesion and ECM molecules, such as CD166, versican, perlecan, and Col4A2, may interfere with cartilaginous differentiation. The decreased expression of CCND1, p16INK4A, and CD166 in HGCCS reflects impairment of cell cycle progression and of cell-cell adhesions in malignant tumors and is of use in the differential diagnosis of CMF.
Romeo
Salvatore
S
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Oosting
Jan
J
Rozeman
Leida B
LB
Hameetman
Liesbeth
L
Taminiau
Antonie H M
AH
Cleton-Jansen
Anne Marie
AM
Bovée
Judith V M G
JV
Hogendoorn
Pancras C W
PC
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002804:Chondroblastoma / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D005260:Female; D005350:Fibroma / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers