Tumor angiogenesis, hepatocyte growth factor, and c-Met expression in endometrial carcinoma

Wagatsuma, S.; Konno, Ryo; Sato, Shinji; Yajima, Akira

doi:10.1002/(sici)1097-0142(19980201)82:3<520::aid-cncr14>3.0.co;2-3

Cited by 97 publications

(97 citation statements)

References 39 publications

(6 reference statements)

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“…Overexpression of c-MET has been shown to be associated with poor prognosis in a number of solid tumors (11)(12)(13)(14)(15). More recently, c-MET expression levels as determined by reverse transcription-PCR and IHC were found to correlate directly with colon cancer stage (16); however, correlation of c-MET expression with recurrent disease or patient survival in colon cancer has not been reported.…”

Section: Discussionmentioning

confidence: 99%

“…It also contains a tyrosine kinase domain that activates signaling pathways involved in cell proliferation, motility, adhesion, and invasion (10). Overexpression of c-MET has been correlated with poor prognosis in cancers such as breast, stomach, liver, endometrium, and nasopharynx (11)(12)(13)(14)(15). More recently, the c-MET expression level in primary colon cancer has been shown to be an important predictive marker for early-stage invasion and regional disease metastasis (16).…”

Section: Introductionmentioning

confidence: 99%

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Epidermal Growth Factor Receptor, c-MET, β-Catenin, and p53 Expression as Prognostic Indicators in Stage II Colon Cancer

Resnick¹,

Routhier²,

Konkin³

et al. 2004

Clinical Cancer Research

183

124

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Purpose: Through the use of molecular markers, it may be possible to identify aggressive tumor phenotypes and tailor therapies to treat them. This approach would be particularly useful for stage II colon cancer. The purpose of this study was to define the prognostic value of epidermal growth factor receptor (EGFR), c-MET, ␤-catenin, and p53 protein expression in TNM stage II colon cancer using tissue microarray technology.Experimental Design: In this study, we retrospectively analyzed, resected, and otherwise untreated paraffin-embedded specimens from 134 consecutive patients with Tumor-Node-Metastasis stage II colonic carcinomas for EGFR, c-MET, ␤-catenin, and p53 protein expression by immunohistochemistry.Results: Thirty-five percent, 77, and 65% of tumors exhibited strong (؉2 and ؉3 immunopositivity) expression of EGFR, c-MET, and ␤-catenin, respectively. Fifty-four percent exhibited nuclear staining for p53 in >10% of the tumor cells. Univariate analysis revealed that increased nuclear p53 expression (P ‫؍‬ 0.001), strong membranous EGFR expression (P ‫؍‬ 0.04), and lymphovascular invasion (P ‫؍‬ 0.01) were significantly related to disease recurrence and that p53 (P ‫؍‬ 0.02) and EGFR (P ‫؍‬ 0.05) expression were associated with decreased survival. Increased nuclear p53 expression also correlated with the presence of distal metastasis (P ‫؍‬ 0.027). No significant association was seen between c-MET expression and prognosis, whereas a strong trend was detected between loss of ␤-catenin (P ‫؍‬ 0.065) expression and poor outcome. Multivariate analysis indicated that p53 (P ‫؍‬ 0.04), EGFR (P ‫؍‬ 0.05), and lymphovascular invasion (P ‫؍‬ 0.03) were independent predictors of recurrence and that p53 (P ‫؍‬ 0.02) and EGFR (P ‫؍‬ 0.01) expression were both associated with poor survival.Conclusions: This retrospective tumor microarray study, restricted to Tumor-Node-Metastasis stage II colon cancer patients who did not undergo adjuvant therapy, supports the use of EGFR and p53 as biological markers, which may assist in predicting disease recurrence and survival.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Epidermal Growth Factor Receptor, c-MET, β-Catenin, and p53 Expression as Prognostic Indicators in Stage II Colon Cancer

Resnick¹,

Routhier²,

Konkin³

et al. 2004

Clinical Cancer Research

183

124

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“…In this way, increased HGF levels contribute to the angiogenesis associated with several human cancers, [35][36][37] and with some other pathologic situations, such as myocardial ischemia, 38 the healing of hepatic wounds, 39 diabetes, 40 diabetic retinopathy, 41 and arthritis and osteoarthritis. 42 Taken together, these results highlight the importance of the HGF/c-met system in vascular remodeling.…”

Section: Discussionmentioning

confidence: 99%

HGF receptor up-regulation contributes to the angiogenic phenotype of human endothelial cells and promotes angiogenesis in vitro

Ding

Merkulova-Rainon

Han

et al. 2003

Blood

160

101

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“…[3][4][5][6][7][8][9] The degree of tumor angiogenesis within individual gynecologic tumors appears to have prognostic importance. Microvessel density (MVD) in primary epithelial carcinomas of the ovary, 10-14 endometrium [15][16][17][18][19] and cervix [20][21][22] has correlated with extent of disease and has inversely correlated with overall survival (OS) or progression free survival (PFS) after initial therapy. Often this relationship to clinical outcome has been found to be independent of important clinical and pathologic prognostic factors.…”

Section: Vascular Endothelial Growth Factor Signaling In Pathogenesismentioning

confidence: 99%

Role of vascular endothelial growth factor inhibitors in the treatment of gynecologic malignancies

Burger

2010

J Gynecol Oncol

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This article reviews the history and current status of vascular endothelial growth factor targeted therapy for the most common gynecologic malignancies -epithelial ovarian, endometrial and cervical cancers. The biologic rationale for targeting vascular endothelial growth factor (VEGF) for these disease sites is well-founded, and pre-clinical studies have supported the development of anti-VEGF agents. Their classification, known mechanisms of action, unique toxicities and clinical development are herein explored, the latter including issues related to study design, disease site and disease setting.

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Tumor angiogenesis, hepatocyte growth factor, and c-Met expression in endometrial carcinoma

Abstract: Both tumor angiogenesis, measured by the microvessel count, and c-Met expression were significant prognostic indicators for patients with endometrial carcinoma.

Cited by 97 publications

References 39 publications

Epidermal Growth Factor Receptor, c-MET, β-Catenin, and p53 Expression as Prognostic Indicators in Stage II Colon Cancer

Epidermal Growth Factor Receptor, c-MET, β-Catenin, and p53 Expression as Prognostic Indicators in Stage II Colon Cancer

HGF receptor up-regulation contributes to the angiogenic phenotype of human endothelial cells and promotes angiogenesis in vitro

Role of vascular endothelial growth factor inhibitors in the treatment of gynecologic malignancies

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