Expression of connective tissue growth factor in cartilaginous tumors.
BACKGROUND
Connective tissue growth factor (CTGF) predominantly is expressed in hypertrophic chondrocytes and its specific receptors are demonstrated on chondrocytic cells. Therefore, CTGF may be involved in the proliferation and/or differentiation of cartilage cells. In the current study, CTGF expression was examined both in chondrosarcoma and enchondroma to clarify the relation between the expression of CTGF and the grade of malignancy.


METHODS
The expression of CTGF and proliferating cell nuclear antigen (PCNA) were analyzed immunohistochemically in 34 cartilaginous tumor specimens. Eighteen tumors were determined to be chondrosarcoma including 8 Grade 1 tumors, 6 Grade 2 tumors, and 4 Grade 3 tumors. The percentage of CTGF positive and PCNA positive cells was quantified using at least 500 cells.


RESULTS
CTGF was expressed in 70.1% of enchondroma cells, 84.0% of Grade 1 chondrosarcoma cells, 53.7% of Grade 2 tumor cells, and 26.8% of Grade 3 tumor cells (rho = -0.501; P = 0.0053). In chondrosarcoma cases, CTGF expression was correlated closely with tumor grade (rho = -0.920; P = 0.0001). There was a strong correlation between PCNA expression and tumor grade (rho = 0.907; P < 0.0001) and a strong negative correlation between CTGF and PCNA expression (rho = -0.493; P = 0.0061). In chondrosarcoma cases, patients with high expression of CTGF (>/= 30%) showed higher overall survival compared with those with low expression (< 30%) (P = 0.004).


CONCLUSIONS
The current study revealed a correlation between the histologic grade of chondrosarcoma and prognosis, and the concomitant association between CTGF immunostaining and tumor grade and prognosis. Therefore, immunohistochemical staining with CTGF is a useful procedure for assessing the tumor grade and clinical course in patients with chondrosarcoma.
Shakunaga
T
T
Department of Orthopaedic Surgery, Faculty of Medicine, Okayama University Medical School, Okayama, Japan.
Ozaki
T
T
Ohara
N
N
Asaumi
K
K
Doi
T
T
Nishida
K
K
Kawai
A
A
Nakanishi
T
T
Takigawa
M
M
Inoue
H
H
D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002812:Chondroma / Q000378:metabolism* / Q000473:pathology; D002813:Chondrosarcoma / Q000378:metabolism* / Q000473:pathology; D055513:Connective Tissue Growth Factor; D005260:Female; D006133:Growth Substances / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000096:biosynthesis*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000032:analysis / Q000096:biosynthesis*; D011237:Predictive Value of Tests; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D016019:Survival Analysis
C526317:CCN2 protein, human; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008934:Mitogens; D018809:Proliferating Cell Nuclear Antigen; D055513:Connective Tissue Growth Factor