Clinical significance of vascular endothelial growth factor‐C and vascular endothelial growth factor receptor 3 in patients with T1 lung adenocarcinoma

Kojima, Hiroshi; Shijubo, Noriharu; Yamada, Gen; Ichimiya, Shingo; Abe, Shosaku; Satoh, Masaaki; Sato, Noriyuki

doi:10.1002/cncr.21366

Cited by 52 publications

(33 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similar to our findings, VEGFR-2 has previously been localized to vessels, supporting BCs (16,17); however, there is only one report of upregulation on vessels (16) and the majority of other studies claim a breast tumor cell localization (22)(23)(24). Similar VEGFR-3 vascular expression data have been reported for BCs (27)(28)(29)(30) and NSCLCs (31); however, others report localization of VEGFR-3 to malignant breast (23,35) or lung cells (19,25,32,33,36,37). VEGFR-2 was originally shown to be restricted to vessels associated with CRCs (15).…”

Section: Relative Vascular Localization Of Vegfr-2 and Vegfr-3 In Prisupporting

confidence: 89%

“…one or the other receptor to tumor vessels (15,16,24,(26)(27)(28)(29)(30)(31), the majority report expression in malignant cells (18)(19)(20)(21)(22)(23)(24)(25)(32)(33)(34)(35)(36)(37). Antibodies from a single source have been used to produce the majority of data, suggesting that tumor cells express VEGFR-2.…”

Section: Relative Vascular Localization Of Vegfr-2 and Vegfr-3 In Primentioning

confidence: 99%

“…However, tumor cell expression has also been reported in 40% to 100% of CRC (20,21), BC (22)(23)(24), and NSCLC (18,19,25). Similarly, some reports confine VEGFR-3 to tumor vessels, primarily lymphatic but also blood endothelium in CRC (26), BC (27)(28)(29)(30), and NSCLC (19,(31)(32)(33), whereas others localize the receptor to tumor cells [CRC (34), BC (23,35), and NSCLC (19,25,32,33,36,37)]. Recently, Petrova et al (38) have provided compelling evidence that poor antibody specificity is likely to be responsible for some of the claims that VEGFR-3 is found on human tumor cells (38).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Vascular Endothelial Growth Factor Receptors VEGFR-2 and VEGFR-3 Are Localized Primarily to the Vasculature in Human Primary Solid Cancers

Smith

Baker

James

et al. 2010

Clinical Cancer Research

201

150

View full text Add to dashboard Cite

Purpose: Vascular endothelial growth factor (VEGF) signaling is key to tumor angiogenesis and is an important target in the development of anticancer drugs. However, VEGF receptor (VEGFR) expression in human cancers, particularly the relative expression of VEGFR-2 and VEGFR-3 in tumor vasculature versus tumor cells, is poorly defined. Experimental Design: VEGFR-2– and VEGFR-3–specific antibodies were identified and used in the immunohistochemical analysis of human primary cancers and normal tissue. The relative vascular localization of both receptors in colorectal and breast cancers was determined by coimmunofluorescence with vascular markers. Results: VEGFR-2 and VEGFR-3 were expressed on vascular endothelium but not on malignant cells in 13 common human solid tumor types (n > 400, bladder, breast, colorectal, head and neck, liver, lung, skin, ovarian, pancreatic, prostate, renal, stomach, and thyroid). The signal intensity of both receptors was significantly greater in vessels associated with malignant colorectal, lung, and breast than adjacent nontumor tissue. In colorectal cancers, VEGFR-2 was expressed on both intratumoral blood and lymphatic vessels, whereas VEGFR-3 was found predominantly on lymphatic vessels. In breast cancers, both receptors were localized to and upregulated on blood vessels. Conclusions: VEGFR-2 and VEGFR-3 are primarily localized to, and significantly upregulated on, tumor vasculature (blood and/or lymphatic) supporting the majority of solid cancers. The primary clinical mechanism of action of VEGF signaling inhibitors is likely to be through the targeting of tumor vessels rather than tumor cells. The upregulation of VEGFR-3 on tumor blood vessels indicates a potential additional antiangiogenic effect for dual VEGFR-2/VEGFR-3–targeted therapy. Clin Cancer Res; 16(14); 3548–61. ©2010 AACR.

show abstract

Section: Relative Vascular Localization Of Vegfr-2 and Vegfr-3 In Prisupporting

confidence: 89%

Section: Relative Vascular Localization Of Vegfr-2 and Vegfr-3 In Primentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Vascular Endothelial Growth Factor Receptors VEGFR-2 and VEGFR-3 Are Localized Primarily to the Vasculature in Human Primary Solid Cancers

Smith

Baker

James

et al. 2010

Clinical Cancer Research

201

150

View full text Add to dashboard Cite

show abstract

“…Nevertheless, as with other tumors, some studies did not report an association between VEGF-A expression and survival. [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.…”

mentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…It correlates with shorter progression free survival (PFS), overall survival (OS) and lymph node metastasis in melanoma [12], and is a poor prognostic factor in nonsmall-cell lung cancer and adenocarcinoma of the lung [13,14]. High levels of VEGF-C expression in gastric cancer tissue imply worse overall prognosis than low VEGF-C levels [15].…”

Section: Introductionmentioning

confidence: 99%

Can vascular endothelial growth factor C expression be of use in predicting surgical stage or prognosis in vulvar cancer ?

Nyberg¹,

Laurila²,

Staff³

et al. 2017

J Cancer Res Ther.

View full text Add to dashboard Cite

Introduction: Nodal metastasis is a main prognostic factor in vulvar cancer. Increased vascular endothelial growth factor C (VEGF-C) expression has been associated with lymph node metastasis and poor prognosis in many cancers. The aim of this retrospective study was to investigate VEGF-C expression pattern in the invasive edge of vulvar cancer and in sentinel lymph node metastasis, and its association with the stage and prognosis. Methods: Tumor and sentinel lymph node samples from 44 patients were evaluated with immunohistochemistry, and the results were linked with the clinicopathological data. Results: Sixty-seven percent of primary tumors and 76% of sentinel lymph node metastases expressed VEFG-C. Positive VEGF-C expression of the primary tumor did not predict surgical Stage or sentinel lymph node involvement. The risk of relapse was not significantly higher with VEGF-C expressing tumors than with VEGF-C negative tumors (RR 2.55, 95% CI 0.66-9.90, p = 0.18). The risk of groin recurrence was significantly lower with VEGF-C positive than negative tumors (RR 0.36, 95% CI 0.16-0.79, p = 0.01). Survival was similar in both groups. No non-sentinel lymph node metastases were found in case of negative VEGF-C expression in the sentinel lymph node metastasis, whereas with positive VEGF-C expression they were found in 5/13 (38%) of cases. Conclusions: Tumoral VEGF-C expression was not associated with higher surgical Stage or poorer prognosis in vulvar cancer. However, absence of its expression in sentinel lymph node metastasis might indicate a low risk for non-sentinel lymph node metastases.

show abstract

Clinical significance of vascular endothelial growth factor‐C and vascular endothelial growth factor receptor 3 in patients with T1 lung adenocarcinoma

Cited by 52 publications

References 47 publications

Vascular Endothelial Growth Factor Receptors VEGFR-2 and VEGFR-3 Are Localized Primarily to the Vasculature in Human Primary Solid Cancers

Vascular Endothelial Growth Factor Receptors VEGFR-2 and VEGFR-3 Are Localized Primarily to the Vasculature in Human Primary Solid Cancers

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

Can vascular endothelial growth factor C expression be of use in predicting surgical stage or prognosis in vulvar cancer ?

Contact Info

Product

Resources

About