Clinical implications of expression of ETS-1 related to angiogenesis in metastatic lesions of ovarian cancers.
OBJECTIVE
ETS-1 has been identified as a proto-oncogene and a transcription factor for tumor angiogenesis, which is essential for the growth, invasion and metastasis of solid tumors. The aim is to investigate the clinical implications of ETS-1 expression in peritoneal metastatic lesions of ovarian cancers.


METHODS
In primary tumors and peritoneal metastatic lesions from 30 patients with stage III ovarian cancers, ETS-1 histoscores and ets-1 mRNA levels were determined by immunohistochemistry and competitive RT-PCR-Southern blot analysis using recombinant RNA, respectively.


RESULTS
Immunohistochemical staining revealed that ETS-1 was expressed in the cancer cells and vascular endothelial cells. ETS-1 histoscores in the endothelial cells and ets-1 mRNA levels were significantly (p < 0.05) increased in 20 of 30 peritoneal metastatic lesions of ovarian cancers. There was a significant correlation between microvessel counts (MVCs) and ETS-1 histoscores in the endothelial cells (p < 0.001) and between MVCs and ets-1 mRNA levels in the primary tumor and the peritoneal metastatic lesion of ovarian cancers (p < 0.001). Furthermore, the 24-month survival rate of patients with significantly increased ets-1 mRNA level (2/20, 10%) was significantly (p < 0.01) lower than that of patients with no change in the level (6/10, 60%) from the primary tumor to the peritoneal metastatic lesion.


CONCLUSIONS
ETS-1 might be associated with peritoneal metastasis dominantly as an angiogenic mediator and additionally as an oncogene product to activate tumor invasion in ovarian cancers.
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Tsukasa-machi, Gifu City, Japan. jf@cc.gifu-u.ac.jp
Jiro
J
Fujimoto
Ikumi
I
Aoki
Hiroshi
H
Toyoki
Sufia
S
Khatun
Eriko
E
Sato
Hideki
H
Sakaguchi
Teruhiko
T
Tamaya
D000328:Adult; D000368:Aged; D005169:Factor VIII / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000556:secondary*; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*
C494041:ETS1 protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D005169:Factor VIII