Jusoh, Mohd Hanifah
(2018)
Osteoclast-specific marker nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 expression in stage III giant cell tumor of the bone.
Masters thesis, Universiti Sains Malaysia.
Abstract
Introduction: Osteoclastic bone resorption and osteolysis with tendency for local recurrence
and pulmonary metastases are a common complication of stage III Campanacci giant cell
tumour of the bone (GCTB). Studies have shown RANKL highly stimulates osteoclastogenesis
through nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1),
which regulates a number of osteoclast-specific genes. Osteoclastogenesis is retarded in
NFATc1 suppression and knock-out embryonic stem cells in vitro. To our knowledge, the
regulation of NFATc1 in osteoclastic resorption in GCTB has not been studied in stage III
GCTB. It is important to fully understand the osteoclast-associated GCTB pathogenesis to
identify a new therapeutic approach by targeting NFATc1 in GCTB treatment. We analyzed
NFATc1 expression immuno-histochemistry of 31 consecutive cases of stage III giant cell
tumour of the bone to determine the clinico-pathological correlation.
Methodology: This observational cross-sectional study evaluated the immunohistochemical
staining for NFATc1 expression in 31 consecutive cases of stage III Campanacci giant cell
tumour of bone (GCTB) operated and treated at Hospital Universiti Sains Malaysia from
January 2004 to December 2017. Expression of NFATc1 was assessed by immunohistochemical
staining in all representative archive tumour sections from each patient. Serial
sections of 5 m was cut and underwent immuno-histochemical staining. NFATc1 expression
over nuclear area of tumor cells was examined using immunohistochemistry. Immunostainings
were evaluated in three randomly chosen microscopic fields using a standard light microscope
at 40 x 100 magnification by two-blinded independent observers. Positivity for NFATc1
expression was assessed according to percentage of 1000 background cells using an image
analysis software (Olympus – U-RFL-T Cell F). The average score from three selected field
was taken for statistical analysis using SPSS version 25.0. Statistical analysis was determined
using independent t-test for different group and considered statistically significant when p
values were less than 0.05.
Results: The mean value of NFATc1 expression obtained as a percentage of 1000 background
cells was 0.81 with standard deviation of 1.48. The range was between 0.0 to 6.33 with a
median of 0.07. Comparison of NFATc1 expression showed higher percentage in recurrence
group with mean of 1.01 (SD 0.68) compared to non-recurrence group with the mean of 0.79
(SD 1.55). The mean difference was 0.22 (-1.06, 1.51). This difference was statistically not
significant with p > 0.005. A comparison of NFATc1 expression showed higher mean value in
lung metastases group which was 2.01 (SD 2.49) compared to 0.58 (SD 1.13) in non-lung
metastases group. The mean difference between the two groups were 1.43 (-1.63, 4.49) which
is statistically not significant with the p value > 0.005.
Conclusions: This study shows not all 31 cases with aggressive GCTB stage III were positively
stained with NFATc1 antibody showing the possibility osteoclast may have not been the main
cells responsible in the bone destruction in GCTB condition. The mean value of NFATc1
expression was found to be statistically not significant when tested against the risk of
pulmonary metastases and recurrence disease, making it not a useful marker to predict the risk
of recurrence and pulmonary metastases in aggressive type of GCTB. This study suggested that
there must be further research to be carried out to understand other different pathways of bone
resorption and osteolysis in GCTB
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