Oncoproteins and proliferation markers in synovial sarcomas: a clinicopathologic study of 19 cases.
OBJECTIVE
The objective of this study was to evaluate synovial sarcomas for the expression of oncogenic proteins (Her2/neu, EGFR, Bcl-2, p53) and proliferation markers (Ki-67, Topoisomerase 2alpha), as possible markers of prognostic significance.


METHODS
From 17 patients with synovial sarcomas 19 tumors (15 primary, 2 recurrent, and 2 metastatic) were selected on the basis of characteristic histology, the expression of at least one epithelial marker, and/or the presence of t(X;18). Adequate follow-up was available in all cases.


RESULTS
The tumors were tested immunohistochemically and were found to express multiple oncogenic proteins. Four of 19 synovial sarcomas (21%) demonstrated nuclear over-expression of p53 protein; 18 of 19 tumors (94%) stained positive for Bcl-2; and 13 of 19 tumors (68%) were immunoreactive with EGFR. Of particular interest was the frequent expression of Her2/neu, an oncogenic protein more commonly observed in epithelial neoplasms. Ten of 19 tumors (52%, 7 monophasic and 3 biphasic) showed positive cytoplasmic and membranous staining with Her2/neu (HercepTest, DAKO). The staining intensity ranged from 1+ to 2+. Cellular expression of Her2/neu was independent of EGFR positivity and showed no association with proliferative activity of the tumors. FISH analysis of eight positive cases showed no evidence of Her2/neu gene amplification. Among the non-metastatic tumors, we found a significant correlation between Ki-67 and Topoisomerase 2alpha. Spearman's correlation co-efficient was 0.86 with P=0.001 ( n=17).


CONCLUSIONS
In this relatively small series of cases, we found no definite correlation between the over-expression of Her2/neu and clinical outcome. The over-expression of p53 was significantly associated with clinical outcome (Fisher's exact test, P=0.02).
Barbashina
Violetta
V
Department of Pathology, UMDNJ-New Jersey Medical School, 185 South Orange Ave., Newark, N.J., USA.
Benevenia
Joseph
J
Aviv
Hana
H
Tsai
James
J
Patterson
Francis
F
Aisner
Seena
S
Cohen
Stanley
S
Fernandes
Helen
H
Skurnick
Joan
J
Hameed
Meera
M
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D013584:Sarcoma, Synovial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53