1: J Exp Clin Cancer Res. 1999 Sep;18(3):305-9. 

Prognostic relevance of TP53 mutations, p53 protein, Ki-67 index and
conventional histological grading in oligodendrogliomas.

Hagel C, Krog B, Laas R, Stavrou DK.

Department of Neuropathology, University Clinic Hamburg Eppendorf, Hamburg,
Germany.

The prognostic value of tumour grading according to WHO, Ki-67 proliferation
index, p53 labelling index and TP53 gene mutations was assessed in 59 patients
(33 oligodendrogliomas WHO grade II, 15 anaplastic oligodendrogliomas, 11
glioblastomas with oligodendroglial growth pattern). The minimal observation
period was 5 years after operation. According to multivariate correlation and
regression tree (CART) analysis grading was the prime prognostic factor (grade
II vs. anaplastic tumours, p < 0.00001). Grade II oligodendrogliomas were
further divided into tumours with and without TP53 mutations (p < 0.05) whereas
anaplastic tumours were subdivided according to age (p < 0.05, cut off at 57
years) and p53 protein accumulation (p < 0.05, cut off at 2%, age 57 years).
Ki-67 labelling index correlated highly significantly with grading but had no
independent prognostic relevance in CART analysis. Accumulation of wild-type p53
protein was not related to bcl-2 expression, a co-expression of p53 and bcl-2
was found at similar frequencies in tumours with or without TP53 mutations (4/12
vs. 3/11). Since accumulation of wild-type and mutant p53 are both associated
with a poor prognosis, it is suggested to include immunohistochemical evaluation
of p53 protein in routine diagnostics of oligodendrogliomas.

PMID: 10606174 [PubMed - indexed for MEDLINE]


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2: J Orthop Res. 1998 Sep;16(5):521-30. 

Expression of cartilage extracellular matrix and potential regulatory genes in a
new human chondrosarcoma cell line.

Chansky H, Robbins JR, Cha S, Raskind WH, Conrad EU, Sandell LJ.

Department of Orthopaedics, University of Washington, Veterans Affairs Medical
Center, Seattle, USA.

A human chondrosarcoma cell line has been established from an aggressive
chondrosarcoma. The cells grow in a monolayer culture (doubling time: 2 days)
and form aggregates. The aggregates consist of a rim of cells surrounding a
hollow core. The cell line exhibits a unique pattern of mRNA expression with
several molecules characteristic of the chondrocyte phenotype. Consistent with
the chondrocyte phenotype, mRNAs encoding types IX and XI collagens were present
along with an abundant expression of mRNAs encoding the core protein of the
cartilage proteoglycans biglycan and aggrecan. No expression of mRNAs encoding
types I or II fibrillar collagens or the proteoglycan decorin was observed.
Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of
[35S]sulfate-radiolabeled material confirmed the translation of proteoglycans
containing glycosaminoglycan chains. The expression of molecules that contribute
to cartilage development and tumorigenesis was examined. The cell line produces
abundant mRNA that encodes transforming growth factor-beta1, a member of a
family of cartilage and bone inductive proteins. The expression of mRNA encoding
two proteins associated specifically with chondrogenesis was detected: Cart-1, a
homeobox protein involved in cartilage differentiation, and CD-RAP, a secreted
molecule restricted under normal conditions to differentiating chondrocytes and
cartilage. Overexpression of p53, a tumor-suppressor gene, was detected. DNA
analysis revealed a loss of heterozygosity at the chromosomal locus encoding
p53, with the deletion of one p53 allele and the mutation of the remaining
allele in both the parent tumor and the cell line. The malignant chondrosarcoma
phenotype may be related to the unique gene expression pattern that is
characteristic in many ways of differentiating chondroblasts, as well as to the
inactivation of the p53 function that could contribute to the proliferative
capacity of the cell line. This cell line may serve as a biological model for
further investigation of the etiology of human chondrosarcomas and for the
synthesis and regulation of cartilage-specific genes.

PMID: 9820274 [PubMed - indexed for MEDLINE]


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