Prognostic Significance of Vascular Endothelial Growth Factor and Its Receptors in Endometrial Carcinoma

Yokoyama, Yoshihiko; Sato, Shigemi; Futagami, Masayuki; Fukushi, Yukiharu; Sakamoto, Tomomi; Umemoto, M; Saito, Yoshiharu

doi:10.1006/gyno.2000.5802

Cited by 58 publications

(41 citation statements)

References 25 publications

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“…VEGF status was also an independent predictor of 5-and 10-year survival. In other studies, however, VEGF expression did not correlate with the incidence of metastases, recurrence, and survival [27][28][29]. The reason for the discrepancies between studies may lie in the varying expression pattern of VEGF in early versus late stage endometrial cancer.…”

Section: Discussionmentioning

confidence: 89%

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

McMeekin

Sill

Benbrook

et al. 2007

Gynecologic Oncology

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Objectives-A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of thalidomide in persistent or recurrent endometrial cancer refractory to cytotoxic chemotherapy, and to correlate angiogenesis biomarker expression with clinical outcome.Methods-Consenting patients were treated until progression or intolerable toxicity with an oral starting dose of 200 mg thalidomide/day that was to increase by 200 mg every 2 weeks to a target dose of 1000 mg/day. Vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), and soluble endothelial protein C receptor (sEPCR) were analyzed by ELISA in pre and post-treatment specimens.Results-Twenty-four of 27 patients enrolled in the study were eligible, of whom 2 reached the target dose, 8 progressed before achieving the target dose and 14 refused or had toxicity that prohibited escalation. Two patients (8.3%) remained progression-free ≥ 6 months. There were 3 (12.5%) with partial responses, 2 (8.3%) with stable disease, 15 (62.5%) with increasing disease, and 4 (16.7%) who were inevaluable for response. Median progression-free survival and overall survival Précis: Thalidomide has minimal activity in chemo-refractory endometrial cancer as judged by the ability to prolong progression-free survival greater than 6 months.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Discussionmentioning

confidence: 89%

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

McMeekin

Sill

Benbrook

et al. 2007

Gynecologic Oncology

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“…However, these markers may not be specific of neoangiogenesis and may not stain all tumour blood vessels to the same degree, and results in terms of prognostic significance are controversial (Gasparini, 1996a, b;Vermeulen et al, 1996;Charpin et al, 1997). More recently, markers of activated endothelial cells, such as CD105 (Seon et al, 1997;Kumar et al, 1999;Fonsatti et al, 2001), Tie-2/Tek (Brown et al, 1995;Mustonen and Alitalo, 1995;Takahashi et al, 1995;Yokoyama et al, 2000) and VEGF (Salven et al, 1996;Peters et al, 1998) receptors as prognostic indicators more suitable for identifying stromal vessels resulting from tumour neoangiogenesis, have been reported. However, in breast carcinomas, the prognostic significance of these markers has not been evaluated in a large series and long-term follow-up.…”

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confidence: 99%

Prediction of metastasis risk (11 year follow-up) using VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 expression in breast cancer (n=905)

Dalès¹,

García²,

Carpentier³

et al. 2004

Br J Cancer

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Neoangiogenesis in tumours contributes to the development of blood-borne metastases, and can be evaluated by markers of activated endothelial cells in preference to panendothelial markers. Our purpose was to document the prognostic significance of VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 immunoexpression in breast carcinoma frozen samples (n ¼ 905, follow-up ¼ 11.7 years). We observed that: (i) CD105 (P ¼ 0.001) and Tie-2/Tek (P ¼ 0.025) (but not VEGF-R1 and VEGF-R2) overexpression correlated with a shorter survival, and were (Cox's model) independent histoprognostic indicators; (ii) only CD105 marked expression correlated (P ¼ 0.035) with a shorter survival of node-negative patients; (iii) three markers -CD105 (P ¼ 0.001), Tie-2/Tek (P ¼ 0.01), VEGF-R1 (P ¼ 0.001), but not VEGF-R2 -correlated with metastatic risk in node-negative patients in univariate analysis; and (iv) VEGF-R1 (P ¼ 0.01) expression correlated with high local recurrence risk. It is concluded that CD105 and to a lesser extent Tie-2/Tek and VEGF-R1, but not VEGF-R2 are endowed with prognostic significance that may be useful for patient monitoring, particularly CD105 expression for selecting node-negative patients for more aggressive postsurgery therapy.

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“…All samples surgically obtained for immunohistochemistry were immediately fixed in formaldehyde and embedded in paraffin. Sections 6 µm thick were routinely passed through xylene and a graded alcohol series and stained for CR by the labelled streptavidin biotin method (LSAB kit; DAKO, Santa Barbara, CA) using anti-CR antibody as reported previously (Yokoyama et al, 2000). Anti-CR antibody was applied for 12 h at 4˚C in a moist chamber.…”

Section: Carbonyl Reductase As a Significant Predictor Of Survival Anmentioning

confidence: 99%

“…2 observers independently evaluated and interpreted the results of immunohistochemical staining, without knowledge of the clinical data of each patient. Immunohistochemical staining was evaluated according to a scoring method reported previously (Yokoyama et al, 2000). Namely, a score was established corresponding to the sum of: (1) the percentage of positive cells (0, 0% immunopositive cells; 1, < 25% positive cells; 2, 26-50% positive cells; and 3, > 50% positive cells); and (2) the staining intensity (0, negative; 1, weak; 2, moderate; 3, high).…”

Section: Carbonyl Reductase As a Significant Predictor Of Survival Anmentioning

confidence: 99%

“…British Journal of Cancer (2001) 85 (7), 1032-1036© 2001 between RLN involvement and the expression of Flt-4 in endometrial cancers and a marginally significant correlation between RLN involvement and VEGF expression, suggesting that VEGF-Flt-4 system might promote lymph-angiogenesis and lymph node metastasis in endometrial cancer (Yokoyama et al, 2000).…”

Section: Carbonyl Reductase As a Prognostic Indicator 1035mentioning

confidence: 99%

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Carbonyl reductase as a significant predictor of survival and lymph node metastasis in epithelial ovarian cancer

et al. 2001

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SummaryWe have recently reported a novel function for carbonyl reductase (CR), namely, its ability to modulate the metastatic potential of malignant mouse cells. Because there are currently no data addressing a similar function for CR in human cancers, the aim of this study was to assess a correlation between survival and metastasis, and CR level in epithelial ovarian cancer. Using anti-CR antibody, immunohistochemical staining was performed on 73 epithelial ovarian cancers, 13 borderline malignant tumours, and 25 benign ovarian tumours for a total of 111 specimens. The combined rate for strongly and weakly positive reactions for CR was 32.0% for benign tumours, 38.5% for borderline malignant tumours, and 61.6% for ovarian cancers. The CR-positive rate was 35.7% (weakly positive alone) for ovarian cancers with retroperitoneal lymph node (RLN) metastasis and 67.8% for those without RLN metastasis (P < 0.05). The 5-year survival rate was 62.7% for the patients with CR-negative cancer and 86.1% for those with CR-positive cancer (P < 0.05). The present results indicate that decreased CR expression in epithelial ovarian cancer is associated with RLN metastasis and poor survival.

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Prognostic Significance of Vascular Endothelial Growth Factor and Its Receptors in Endometrial Carcinoma

Cited by 58 publications

References 25 publications

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

Prediction of metastasis risk (11 year follow-up) using VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 expression in breast cancer (n=905)

Carbonyl reductase as a significant predictor of survival and lymph node metastasis in epithelial ovarian cancer

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