Comparison of the prognosis indication of VEGFR-1 and VEGFR-2 and Tie2 receptor expression in breast carcinoma

Meunier-Carpentier, Séverine; Dalès, Jean-Philippe; Djemli, Amina; Garcia, Stéphane; Bonnier, Pascal; Andrac-Meyer, Lucile; Lavaut, Marie‐Noëlle; Allasia, Claude; Charpin, Colette

doi:10.3892/ijo.26.4.977

Cited by 27 publications

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“…We analyzed several markers, such as CD105, Tie2, CD34, VEGF-R1 and -R2, CD146, [40][41][42][43][44] in frozen tissue to evaluate angiogenesis in breast cancers associated with poor prognosis. In this study on fixed tissue, only CD146 proved to be of prognostic significance when evaluated on TMAs in univariate analysis, and not in logistic regression.…”

Section: Discussionmentioning

confidence: 99%

A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays

Charpin

Secq

Giusiano

et al. 2009

Intl Journal of Cancer

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Quantitative immunocytochemical assays of 1,200 breast carcinomas were assessed after construction of tissue microarrays. A total of 42 markers were evaluated for prognostic significance by univariate log rank test (mean follow‐up, 79 months), using quantitative scoring by an image analysis device and specific software. Complete data were obtained for 924 patients, for whom 27 of the 42 markers proved to be significant prognostic indicators. Analysis of these 27 markers by logistic regression showed that 18 (cMet, CD44v6, FAK, moesin, caveolin, c‐Kit, CK14, CD10, P21, P27, pMAPK, pSTAT3, STAT1, SHARP2, FYN, ER, PgR and c‐erb B2), and 15 when ER, PgR and c‐erb B2 were excluded, were 80.52% and 78.9% predictive of disease outcome, respectively. The immunocytochemical assays on 4 micron thick sections of fixed tissue are easy to handle in current practice and are cost‐effective. Quantitative densitometric measurement of immunoprecipitates by computer‐assisted devices from digitized microscopic images allows standardized high‐throughput “in situ” molecular profiling within tumors. It is concluded that this 15 marker immunohistochemical signature is suitable for current practice, since performed on paraffin sections of fixed tumor samples, and can be used to select patients needing more aggressive therapy, since this signature is about 80% predictive of poor clinical outcome. Also, the markers included in the signature may be indicative of tumor responsiveness to current chemotherapy or suggest new targets for specific therapies. © 2008 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays

Charpin

Secq

Giusiano

et al. 2009

Intl Journal of Cancer

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“…[26][27][28][29][30] Another factor from the VEGF family that has been associated with poorer survival in patients with lung cancer is VEGF-C. [31][32][33][34] The analysis of VEGF family receptors has not provided conclusive evidence of their effects on the survival of Original Article cancer patients, except for VEGFR3/Flt-4, the expression of which has been associated with poorer survival in patients with lung cancer 32,34,35 and with other tumors. [36][37][38] However, although some studies of VEGFR1/Flt-1 and VEGFR2/Flk-1 demonstrated a relation between the expression of these 2 receptors and poorer survival, 16 others did not 14,39,40 ; and in the study by Zhukova et al, 41 VEGFR1 expression was associated to better survival. Because of the relevance of the VEGF family in tumor development and progression, we analyzed the expression of VEGF-A, VEGF-B, VEGF-C, and VEGF-D as well as the expression of their receptors (VEGFR1, VEGFR2, and VEGFR3), in tissue samples to describe their relations with survival in patients with lung cancer patients.…”

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confidence: 99%

Prognostic significance of the expression of vascular endothelial growth factors A, B, C, and D and their receptors R1, R2, and R3 in patients with nonsmall cell lung cancer

Pau¹,

Arias

Peláez

et al. 2009

Cancer

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BACKGROUND:Lung cancer is the leading cause of cancer death in the world. The objective of this study was to investigate the expression of vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) in patients with nonsmall cell lung cancer (NSCLC) and its correlation with the prognosis for patients with lung cancer.METHODS:The expression status of VEGFs and VEGFRs was examined in 48 nonconsecutive specimens of primary lung cancer by immunohistochemistry. Correlations between the expression of VEGFs and VEGFRs and clinicopathologic parameters were analyzed.RESULTS:Nineteen of 48 samples (39.6%) were moderately/highly immunoreactive for VEGF‐A, 6 samples (12.5%) were reactive for VEGF‐B, 14 samples (29.2%) were reactive for VEGF‐C, 11 samples (22.9%) were reactive for VEGF‐D, 20 samples (41.7%) were reactive for VEGFR1, 26 samples (54.2%) were reactive for VEGFR2, 20 samples (41.7%) were reactive for VEGFR3, and 19 samples (39.6%) were reactive for nuclear expression of VEGFR3. Patients with moderate/high VEGF‐C, VEGFR1, and VEGFR2 expression had worse survival, whereas patients with moderate/high VEGF‐D and nuclear VEGFR3 expression had better survival. After adjusting according to tumor stage, VEGF‐B and VEGF‐D expression had a significant correlation with worse survival in patients with stage I and II disease. Patients with stage III and IV disease who had VEGFR1 and VEGFR2 expression had worse survival, whereas the expression of VEGF‐D was correlated significantly with better survival. Finally, stage, VEGF‐D expression, and VEGFR1 expression were significantly independent prognostic predictors.CONCLUSIONS:The results of the current study indicated that the over‐expression of VEGFs and VEGFRs plays an important role in the survival of patients with NSCLC. The inclusion of angiogenic factors in the standard pathologic study of lung cancer may improve the clinical evaluation of patients with NSCLC. Cancer 2009. © 2009 American Cancer Society.

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“…Various GFRs are implicated in angiogenesis, particularly the VEGFR family of receptor tyrosine kinases (27). VEGFR1 and VEGFR2 are closely related receptor tyrosine kinases, and VEGFR2 serves a broader role than VEGFR1 in angiogenesis (28).…”

Section: Sema6d and Its Receptor Plexin-a1 Are Highly Expressed In Vamentioning

confidence: 99%

Expression of semaphorin 6D and its receptor plexin-A1 in gastric cancer and their association with tumor angiogenesis

Chen

et al. 2016

Oncology Letters

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Abstract. The semaphorin and plexin family of ligands and receptor proteins provides important axon growth and guidance cues required for development. In recent years, studies have expanded their role in the regulation of cardiac morphogenesis and tumorigenesis. However, the mechanism responsible for their role in regulating cancer development and progression has not been clarified. In the present study, semaphorin 6D (Sema6D) and its receptor plexin-A1 were identified to be expressed at high levels in vascular epithelial cells within gastric cancer, and were positively correlated with vascular endothelial growth factor receptor 2 (VEGFR2). These findings verify our hypothesis that Sema6D and plexin-A1 may be closely associated with tumor angiogenesis. Combined with experimental observations in the MGC803 gastric cancer cell line, it was observed that knocking down plexin-A1 signaling led to a decreased expression of VEGFR2 at the messenger RNA and protein levels. Sema6D recognized and activated plexin-A1, which subsequently activated its downstream target, VEGFR2. The activation of VEGFR2 functioned as a positive regulator of tumor angiogenesis. Our data provided an understanding of the complex signaling cascades involved in the angiogenesis-related pathway in tumor cells. In light of our observations, pharmacological interventions targeting Sema6D/plexin-A1/VEGFR2 signaling may potentially be used as a target for the development of novel anti-angiogenic drugs in gastric cancer. IntroductionThe semaphor in fam ily is a la rge super-protei n fa m ily cont a in ing secreted, t ra nsmembra ne a nd glycosylphosphatidylinositol-linked proteins, and it has been divided into eight hypotypes based on their structures and amino acid sequence similarity: Invertebrate semaphorins consist of classes 1 and 2, while classes 3-7 are vertebrate semaphorins (with the exception of class 5C semaphorins, which are encoded by viral genomes) (1). The semaphorin family was initially identified to be involved in mediating axonal guidance in the developing nervous system (2). Certain members of the semaphorin family have been also shown to exert diverse and important functions in other physiological processes, including heart morphogenesis (3,4), vascular growth (5), immune cell regulation (6) and tumor progression (7,8). Important regulatory functions of certain members of the semaphorin family within tumor angiogenesis have been reported. For example, semaphorin 3A (Sema3A) inhibits angiogenesis through competition for vascular endothelial growth factor (VEGF) (9), and Sema3B has also been indicated as a putative tumor suppressor that inhibits tumor growth and angiogenesis (10). By contrast, Sema3C presumably may promote angiogenesis by stimulating integrin phosphorylation and VEGF120 secretion (11), and Sema4D has been demonstrated to serve a role in tumor-induced angiogenesis (12).Sema6D, mapped on chromosome 2, is the best characterized factor of the class 6 semaphorins, which are single-pass membrane-bound semaphorins (13). It wa...

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Comparison of the prognosis indication of VEGFR-1 and VEGFR-2 and Tie2 receptor expression in breast carcinoma

Cited by 27 publications

References 0 publications

A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays

A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays

Prognostic significance of the expression of vascular endothelial growth factors A, B, C, and D and their receptors R1, R2, and R3 in patients with nonsmall cell lung cancer

Expression of semaphorin 6D and its receptor plexin-A1 in gastric cancer and their association with tumor angiogenesis

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