Winter Meeting 2011 - The Pathological Society of Great Britain ...

P77
P63 Does Not Regulate Brachyury in Chordomas and
Osteosarcomas
P N Pillay 1 ; MF Fernanda 2 ; F Berisha 2 ; R Tirabosco 2 ;
AM Flanagan 1
1 UCL Cancer Institute and Royal National Orthopaedic Hospital, London,
United Kingdom; 2 Royal National Orthopaedic Hospital, London, United
Kingdom
Background: Chordomas are rare tumours sited along the axis and characterised by the
expression of brachyury, a transcription factor, which under physiological conditions
is only expressed in the developing skeleton. The mechanism by which brachyury
expression is regulated in mammalian cells is unknown. It was therefore of interest to
read recently that the deltaNP63 isoform is responsible for the transcriptional regulation
of brachyury in murine development and osteosarcomas. Purpose: The aim of this study
was to investigate whether expression of P63 accounted for the aberrant expression
of brachyury in human chordomas and to determine if brachyury were expressed in
osteosarcomas. Methods:We screened 26 chordomas and the UCH1 human chordoma
cell line for P63 mRNA expression by RT-PCR initially using a PAN P63 primer set, and
thereafter algorithmically using sets of transcript specific primers for the TAP63 and
deltaNP63 transcripts. All 27 cases showed expression of pan P63 but were negative for
the deltaNP63 transcript. Immunohistochemistry using the panP63 antibody4A4 was
performed on a tissue microarray with 50 chordomas including the 26 cases that were
analysed by RT-PCR. None of the cases showed P63 expression. In addition we screened
a tissue microarray, containing sections of 200 osteosarcomas, for the expression of
both brachyury and deltaNP63. None of the cases showed immunoreactivity for these
antibodies. Conclusion: While it is intriguing that P63 is involved in the transcriptional
regulation of brachyury in murine embryos we have excluded this molecule as a
transcriptional regulator of brachyury in chordomas. Furthermore, neither brachyury nor
P63 are expressed in human osteosarcomas. In summary, the finding that the deltaNP63
isoform in mice regulates the expression of brachyury cannot be translated to humans in
the context of chordoma and osteosarcoma development. Supported by PathSoc grant.
P79
Diseased Intervertebral Discs Tissues Express a marker of
Infection
P EB Abdellatif; AJ Freemont
The University of Manchester, Manchester, United Kingdom
PURPOSE OF THE STUDY: Low Back Pain affects around 40% of people in the UK at
some point in their lives. It is an expensive disease which costs the UK alone over £5-12
billion per annum and 180 million working days. Some studies reported a link between
infection with Propionibacterium acnes and low back pain, but this has not been proven.
We found Procalcitonin (PCT) protein which is a well known infection marker and
widely produced from different tissues during infection to be a helpful diagnostic marker
for osteoarticular infections. We hypothesised that were intervertebral disc degeneration
(IVDD) an osteoarticular infection disc cells would express procalcitonin.
METHODS: We studied 13 cases of lumbar IVD disease by procalcitonin
immunohistochemistery. Immunoelectron microscopic studies were done to detect the
subcellular localization of PCT in IVD tissues. Results were compared to procalcitonin
expression in other chondroid tissues as chondrocytes in diseased synovium and in recent
fractures.
SUMMARY OF RESULTS: We found that PCT is widely expressed in IVD cells and
matrix. There was an expression of PCT in nucleus pulposus cells and its pericellular
matrix that we have not seen with other cells. This distribution has been studied by
immunoelectron microscopy which showed that PCT was found in intracellular vesicles
and had a zonal distribution in matrix.
CONCLUSION: This unexpected result could indicate that IVDD is caused by infection
but in the absence of any other supporting evidence it is more likely that PCT expression
in IVD tissues may indicate that PCT has a role in IVD matrix and cellular degeneration.
These findings need further study to find out if PCT has a role in IVD cell metabolism or
a specific role in IVDD.
P78
Is It Possible to Diagnose Septic Arthritis with High Specificity
and Sensitivity by Using Procalcitonin in a Novel Way?
P EB Abdellatif; AJ Freemont
University of Manchester, Manchester, United Kingdom
PURPOSE OF THE STUDY: Septic arthritis is a challenging medical emergency which
needs an urgent diagnosis. No gold standard is available for diagnosing septic arthritis. A
novel diagnostic test with high specificity and sensitivity is required. Serum procalcitonin
(PCT) is a biomarker which has been used widely to diagnose infection but although
present in the serum of patients with septic arthritis it is not present in high levels in
synovial fluid. There are controversial results regarding its efficacy in diagnosing septic
arthritis. This work investigates a novel aspect of PCT expression in septic arthritis and
reviews the literature around PCT expression and septic arthritis.
METHODS: 64 synovial biopsies from patients with established diagnosis of different
arthropathies were studied by PCT immunohistochemistry. The number of neutrophils
expressing PCT together, with other parameters, were assessed in each biopsy and used to
generate receiver operating characteristic (ROC) curves that enable septic arthritis to be
distinguished from other arthropathies.
SUMMARY OF RESULTS: PCT is expressed by cells in synovium, and (ROC) curves
derived data have produced a diagnostic parameter of septic arthritis with 100% sensitivity
and 80% specificity. In addition, within infected joints fibrin attached to the synovial
surface stains for PCT, suggesting that sequestration of PCT by fibrin might explain why
in septic arthritis PCT can be identified in serum but not in synovial fluid.
CONCLUSION: PCT immunohistochemistry could be used as a diagnostic test for septic
arthritis. Fibrin binding of PCT may explain the discrepant results around the utility of
serum and synovial fluid PCT as diagnostic test in septic arthritis.
P80
Podoplanin Expression in Adamantinoma of Long Bones and
Osteofibrous Dysplasia
P T Kashima 1 ; A Dongre 1 ; R Taylor 1 ; AM Flanagan 2 ;
PCH Hogendoorn 3 ; NA Athanasou 1
1 Nuffield Orthopaedic Centre, Oxford, United Kingdom; 2 Royal National
Orthopaedic Hospital, London, United Kingdom; 3 Leiden University,
Leiden, Netherlands
Adamantinoma of long bones (ALB) and osteofibrous dysplasia (OFD) are rare osteolytic
bone tumours that principally arise in the tibia. Both ALB and OFD contain epithelial
and stromal elements. ALB needs to be distinguished from metastatic cancer and OFD
contains fibrous dysplasia (FD)-like areas. Podoplanin, a transmembrane glycoprotein
expressed by osteocytes, has been reported in a number of biphasic tumours including
adamantinoma of the jaw. In this study we assessed podoplanin expression in ALB, OFD,
fibrous dysplasia (FD) and metastatic cancer.
42 cases of ALB and OFD were stained by immunohistochemistry for expression of
podoplanin and epithelial cell markers.
Podoplanin was detected in epithelial cells of ALB as well as in scattered fibroblastlike
stromal cells in both ALB and OFD. Podoplanin expression in FD was not seen
intertrabecular fibrous tissue. Podoplanin expression was not seen in epithelial cells in
(non-squamous) metastatic carcinomas. Podoplanin expression was noted in osteocytes
but not in osteoblasts of bone trabeculae in ALB, OFD, FD and metastatic carcinoma.
The finding of a common osteocyte marker on OFD/ALB stromal cells is in keeping with
a close histogenetic relationship between OFD and ALB. This may reflect the prominence
of fibro-osseous proliferation in these tumours. Expression of podoplanin in an osteolytic
tumour of the tibia may be a useful diagnostic discriminant in distinguishing in ALB from
metastatic carcinoma and in the differential diagnosis of OFD from FD.
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