Changes in the expression of E-cadherin repressors, Snail, Slug, SIP1, and Twist, in the development and progression of ovarian carcinoma: the important role of Snail in ovarian tumorigenesis and progression.
Changes in the expression of E-cadherin have been reported to be important in the tumorigenesis and progression of epithelial ovarian carcinoma. To further examine the mechanisms regulating E-cadherin expression in ovarian tumorigenesis, we investigated the immunohistochemical expression of transcriptional repressors for E-cadherin, such as Snail, Slug, SIP1, and Twist, in the ovarian surface epithelium (OSE) and 95 cases of epithelial ovarian tumors. OSE cells were negative for SIP1 and Slug, whereas weak expression of Snail and Twist was observed in 8 (73%) and 3 (27%) cases, respectively. Of 95 ovarian tumors, the expression of Snail, Slug, SIP1, and Twist increased stepwise in benign, borderline, and malignant tumors. Among them, the expression of Snail showed significantly inverse correlation with that of E-cadherin. Regarding the FIGO stage classification, the expressions of Snail and Twist were significantly increased in advanced cases. The prognosis of ovarian carcinoma patients positive for Snail expression was poorer than that of negative patients. Our results indicate that the expression of E-cadherin transcriptional repressors increased with malignancy in ovarian epithelial neoplasms and that the expression of E-cadherin and its negative regulators is altered during ovarian cancer development and peritoneal dissemination.
Yoshida
Junko
J
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Horiuchi
Akiko
A
Kikuchi
Norihiko
N
Hayashi
Akiko
A
Osada
Ryosuke
R
Ohira
Satoshi
S
Shiozawa
Tanri
T
Konishi
Ikuo
I
D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D015820:Cadherins / Q000032:analysis / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000737:chemistry / Q000166:cytology / Q000473:pathology; D016601:RNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D012097:Repressor Proteins / Q000032:analysis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000032:analysis / Q000378:metabolism
D014408:Biomarkers, Tumor; D015820:Cadherins; C108381:GEMIN2 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1