Overexpression of p53 and rare genetic mutation in mesenchymal chondrosarcoma.
Mesenchymal chondrosarcoma is extremely rare and accounts for less than 2% of all chondrosarcomas. The pathogenesis and the molecular genetic events which contribute to the development of mesenchymal chondrosarcoma are not well elucidated, due in part to the lack of sufficient tumor tissue available. To characterize the involvement of the p53 gene abnormality in this disease, we analyzed expression and sequence alteration of p53 by immunohistochemical analysis of the protein expression and quantitative DNA/PCR and PCR-SSCP assays of the gene in 33 paraffin-embedded tissue specimens. Immunohistochemical analysis demonstrated that 19 (61.3%) of 31 had nuclear overexpression of p53 while 7 (22.6%) showed cytoplasmic expression. The remaining 5 (16.1%) were negative for p53 staining. The nuclear positivity of p53 was observed within a range of 22-64% (mean 37.3%) of tumor cells and showed a positive staining in mesenchymal components as well as chondroid components. Quantitative DNA/PCR analysis revealed that 6 (18.2%) of the 33 specimens carried significantly reduced or undetectably low levels of p53 indicating the genomic deletion of the gene in these tumors. In contrast, however, DNA/PCR-SSCP analysis failed to detect any types of mutations resulting in amino acid substitution within exons 5-9 regions of the gene. Taken together, our data suggests that genetic alteration of p53 is a relatively rare event in mesenchymal chondrosarcomas but substantial fraction of this type of tumors carries abnormal overexpression of p53, which might result from as yet unidentified epigenetic mechanism(s).
Park
Y K
YK
Department of Pathology, Kyung Hee University Hospital, Dongdaemoon-ku, Seoul 130-702, Korea. damia@cholian.net
Park
H R
HR
Chi
S G
SG
Kim
C J
CJ
Sohn
K R
KR
Koh
J S
JS
Kim
C W
CW
Yang
W I
WI
Ro
J Y
JY
Ahn
K W
KW
Joo
M
M
Kim
Y W
YW
Lee
J
J
Yang
M H
MH
Unni
K K
KK
D018211:Chondrosarcoma, Mesenchymal / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D016612:Paraffin Embedding; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53