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.
Fujimoto
Jiro
J
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Tsukasa-machi, Gifu City, Japan. jf@cc.gifu-u.ac.jp
Aoki
Ikumi
I
Toyoki
Hiroshi
H
Khatun
Sufia
S
Sato
Eriko
E
Sakaguchi
Hideki
H
Tamaya
Teruhiko
T
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