Prognostic Factors of Stage IV Epithelial Ovarian Cancer: A Multicenter Retrospective Study

Akahira, Jun Ichi; Yoshikawa, Hiroyuki; Shimizu, Yoshio; Tsunematsu, Ryuichiro; Hirakawa, Tsubasa; Kuramoto, Hiroyuki; Shiromizu, Kenji; Kuzuya, Kazuo; Kamura, Toshiharu; Kikuchi, Yoshihiro; Kudoh, Shoji; Yamamoto, Kaichirô; Sato, Shinji

doi:10.1006/gyno.2001.6172

Cited by 116 publications

(91 citation statements)

References 21 publications

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“…The VEGF-independent increase of gelatinases in the lungs of tumor-bearing mice compared with healthy mice, in our model, is worth noting. This can be explained by the fact that ovarian tumors secrete several other factors besides VEGF, which can induce the production of host proteolytic enzymes (3), and the pleural cavity is the most common extraperitoneal site to which stage IV epithelial ovarian cancer preferentially metastasizes (6). Increased host proteolytic activity would therefore endorse pleural cavity colonization by ovarian tumor cells.…”

Section: Discussionmentioning

confidence: 99%

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Vascular Endothelial Growth Factor Stimulates Organ-Specific Host Matrix Metalloproteinase-9 Expression and Ovarian Cancer Invasion

Belotti

Calcagno

Garofalo

et al. 2008

Molecular Cancer Research

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Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP) regulate each other, contributing to tumor progression. We have previously reported that MMP9 induces the release of tumor VEGF, promoting ascites formation in human ovarian carcinoma xenografts. The aim of this study was to investigate whether tumor-derived VEGF regulated the expression of gelatinase by the stroma, influencing the invasive properties of ovarian tumors. Tumor variants derived from 1A9 human ovarian carcinoma, stably expressing VEGF 121 in the sense (1A9-VS-1) and antisense orientations (1A9-VAS-3), were used. In vivo, zymographic analysis of tumors from 1A9-VS-1 implanted in the peritoneal cavity of nude mice showed higher levels of gelatinases, particularly murine MMP9, indicating that VEGF stimulates host expression of the matrix-degrading enzyme. Murine MMP9 expression was also high in the ovaries of mice bearing 1A9-VS-1 tumors. The effect on host MMP9 activity was organ-specific. The levels of host pro-MMP9 in ovaries correlated with the plasma levels of tumor VEGF and with the selective invasion of the ovaries. Induction of host MMP9 expression in tumors and ovaries was independent of the site of tumor growth as it was seen in mice carrying both intraperitoneal and subcutaneous tumors. The anti-VEGF antibody bevacizumab (Avastin) inhibited MMP9 expression and tumor invasion in the ovaries of mice bearing 1A9-VS-1 tumors. These findings point to a complex cross-talk between VEGF and MMPs in the progression of ovarian tumor and suggest the possibility of using VEGF inhibitors to affect MMP-dependent tumor invasion.

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Section: Discussionmentioning

confidence: 99%

“…Distant lymphatic and/or hematogenous spread of ovarian carcinoma can involve any organ, including the brain (4) and the liver (5), although this is much less frequent. The pleural cavity is the most common site for stage IV disease (6).…”

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial Growth Factor Stimulates Organ-Specific Host Matrix Metalloproteinase-9 Expression and Ovarian Cancer Invasion

Belotti

Calcagno

Garofalo

et al. 2008

Molecular Cancer Research

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“…Immunohistochemical analysis was performed using the streptavidin -biotin amplification method using a Histofine Kit (Nichirei, Tokyo, Japan), and have been previously described in detail (Akahira JI et al, 2001. Oestrogen receptorbinding fragment associated gene 9 antibody was a rabbit polyclonal antibody against a GST-EBAG9 fusion protein .…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Epithelial ovarian cancer is the leading cause of death from gynaecological malignancies in the great majority of developed countries Akahira JI et al, 2001,). Sex steroid hormones have been implicated in the aetiology and/or progression of some epithelial ovarian cancers.…”

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confidence: 99%

Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer

Aoki

Suzuki

et al. 2004

Br J Cancer

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Oestrogen receptor-binding fragment associated gene 9, EBAG9, is an oestrogen-responsive gene that was identified in MCF-7 human breast carcinoma cell line. It is identical to RCAS 1, a cancer cell surface antigen possibly involved in immune escape. In the present study, we examined the expression of EBAG9/RCAS1 in human epithelial ovarian cancer using immunohistochemistry, immunoblotting and reverse transcription -polymerase chain reaction (RT -PCR). A total of 90 epithelial ovarian cancer cases were examined immunohistochemically by means of the antibodies for EBAG9 and ERa. The correlation between EBAG9 immunoreactivity and clinicopathological parameters was examined. mRNA expression of EBAG9 and ERa were evaluated by RT -PCR in 22 cases. The expression for EBAG9 and ERa was examined by immunoblotting in 12 ovarian cancer cell lines. EBAG9 immunoreactivity was detected in the surface and cytoplasm of carcinoma cells in 46 out of 90 cases (51.1%). EBAG9 expression was significantly higher in serous histology (P ¼ 0.0402) and advanced disease (P ¼ 0.0206). No significant relationship was detected between EBAG9 immunoreactivity and overall survival (P ¼ 0.689). There was a highly significant correlation between EBAG9 and ER immunoreactivity (Po0.0001). The EBAG9 mRNA was detected in 20 out of 22 cases. In all of the cases that were positive for ERa mRNA, they were also positive for EBAG9 mRNA. Immunoreactive band corresponding to EBAG9 was detected in 11 out of 12 of ovarian cancer cell lines, and was consistent with ERa expression. In conclusion, the wide distribution of EBAG9 and its relation to advanced disease suggest that this protein may play important roles in epithelial ovarian cancer.

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“…In women with advanced epithelial ovarian cancer, several studies have identified age, performance status, histological cell type, stage, histological grade, residual tumour size and presence of ascites as independent prognostic factors. [14][15][16][17] None of the previous reports have investigated bowel obstruction at presentation as a prognostic factor. Therefore, this investigation presents the experience in a single institution with women who have ovarian cancer and present with bowel obstruction in an attempt to characterise the impact on prognosis, if any, of bowel obstruction at the time of primary presentation.…”

Section: Introductionmentioning

confidence: 99%

Impact of bowel obstruction at the time of initial presentation in women with ovarian cancer

Rauh‐Hain

Carmen

Horowitz

et al. 2009

BJOG

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Objective To determine whether the presence of bowel obstruction at the time of initial presentation has any prognostic significance in these women.Design Retrospective cohort study.Setting Dedicated gynaecological oncology service of a large tertiary institution.Population Women who had a bowel obstruction as part of their initial presentation of ovarian cancer were identified between 1995 and 2007. Each woman was matched with four control women (with disease but no obstruction).Methods Women with disease were compared with controls to determine the impact, if any, of bowel obstruction at presentation. Several prognostic variables including bowel obstruction were also evaluated in a Cox proportional hazard model. Main outcome measures Progression-free survival (PFS) and overall survival (OS).Results Forty-eight women with disease and 192 controls were identified during the study period. The median follow-up period was 19 months among women with disease versus 20 months in controls. No differences were seen in demographics and clinical characteristics of the women. Optimal cytoreduction rate was similar between the two groups (75% versus 78%, P = 0.7). Patients with bowel obstruction had a shorter PFS and OS compared with controls [19 months versus 21 months (P = 0.01) and 22 versus 35 months (P = 0.008)], respectively. Bowel obstruction at presentation was an independent prognostic variable with a hazard ratio of 1.5 (P = 0.009). Other prognostic variables were age, stage and extent of surgical cytoreduction.Conclusions Bowel obstruction at the time of initial presentation is an adverse prognostic factor in women with ovarian cancer.

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Prognostic Factors of Stage IV Epithelial Ovarian Cancer: A Multicenter Retrospective Study

Cited by 116 publications

References 21 publications

Vascular Endothelial Growth Factor Stimulates Organ-Specific Host Matrix Metalloproteinase-9 Expression and Ovarian Cancer Invasion

Vascular Endothelial Growth Factor Stimulates Organ-Specific Host Matrix Metalloproteinase-9 Expression and Ovarian Cancer Invasion

Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer

Impact of bowel obstruction at the time of initial presentation in women with ovarian cancer

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