Prognostic significance of apoptosis in synovial sarcoma: correlation with clinicopathologic parameters, cell proliferative activity, and expression of apoptosis-related proteins.
bcl-2 overexpression in synovial sarcomas has been recently reported. Although it is widely known that bcl-2 suppresses apoptosis in various cells, there are no studies that have examined the significance of apoptosis in synovial sarcoma. In the present study, we visualized apoptotic tumor cells by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) method in 49 cases of primary synovial sarcoma. The degree of apoptosis was analyzed in relation to several clinicopathologic parameters, cell proliferative activity, and immunohistochemical expression of apoptosis-related proteins, including bcl-2, bax, bcl-x, bak, p53, p21 (WAF1/CIP1), Fas, and Fas ligand. TUNEL index (TUNEL-I) significantly correlated with the mitotic index (MI) (ñ = 0.60, P < .0001) and Ki-67 labeling index (MIB1-I) (ñ = 0.52, P = 0.0005). There was a highly significant association between high TUNEL-I value (>.8%) and poor prognosis (log-rank test; P < .0001). Many synovial sarcomas were diffusely positive for bcl-2 family proteins (bcl-2, bax, bcl-x, and bak) and were negative or only sporadically positive for Fas, Fas ligand, p53, and p21 (WAF1/CIP1) proteins. The results indicated that increased rate of apoptosis in primary synovial sarcoma was considered to be an indicator of poor prognosis. In addition, apoptosis in synovial sarcoma may be controlled by multiple apoptosis-regulating mechanisms, including the bcl-2 family.
Department of Pathology, National Kyushu Cancer Center, Fukuoka, Japan.
S
S
Kawauchi
T
T
Fukuda
Y
Y
Oda
T
T
Saito
A
A
Oga
M
M
Takeshita
K
K
Yokoyama
H
H
Chuman
Y
Y
Iwamoto
K
K
Sasaki
M
M
Tsuneyoshi
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D002455:Cell Division; D002648:Child; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013584:Sarcoma, Synovial / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D012983:Soft Tissue Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor / Q000378:metabolism
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor