Expression of vascular endothelial growth factor A, B, C, and D in oral squamous cell carcinoma

Shintani, Satoru; Li, Chunnan; Ishikawa, Tohru; Mihara, Mariko; Nakashiro, Koh‐ichi; Hamakawa, Hiroyuki

doi:10.1016/s1368-8375(03)00127-1

Cited by 122 publications

(120 citation statements)

References 26 publications

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“…21 Also, other reports implied the prognostic significance of the positive expression of this protein for the clinical outcome. [22][23][24] To our knowledge, this is the first study examining the correlation of COX-2 with VEGF-C in patients with head and neck squamous cell carcinoma. The implication of COX-2 to lymphangiogenesis is possible, since COX-2 is a pleiotropic enzyme that mediates many cellular functions.…”

Section: Discussionmentioning

confidence: 93%

COX-2 expression correlates with VEGF-C and lymph node metastases in patients with head and neck squamous cell carcinoma

2005

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Recent observations suggest an implication of the cyclooxygenase-2 (COX-2) in tumor lymphangiogenesis through an upregulation of vascular endothelial growth factor-C expression. It is unknown whether this mechanism also acts in squamous cell carcinoma of the head and neck region. We performed a retrospective study of 70 patients with head and neck squamous cell carcinoma in order to investigate whether COX-2 immunohistochemical expression correlates with vascular endothelial growth factor-C expression. We also examined the association of the expression of these molecules with clinicopathologic parameters (especially lymph node status) and outcome for these patients. We performed immunostaining on formalin-fixed, paraffinembedded tissue sections by the routine streptavidin-biotin peroxidase labeled procedure. Increased cyclooxygenase-2 expression was observed in 30 of the 68 tumor samples (44%), while high vascular endothelial growth factor-C expression occurred in 26 of the 68 tumor samples (38%). High expression of the two proteins was correlated with the presence of lymph node metastasis at the time of diagnosis, and the observed association was even stronger when there was overexpression for both the antibodies (Po0.001). High expression of vascular endothelial growth factor-C, but not of COX-2 was correlated with increased mortality in patients with oral-larynx squamous cell carcinoma. When multivariate Cox regression model was applied, the presence of lymph node metastasis at the time of diagnosis, combined with overexpression of both the antibodies, was the only independent prognostic factor for mortality of these patients. Our results suggest that a lymphangiogenic pathway, in which COX-2 overexpression stimulates vascular endothelial growth factor-C upregulation, probably exists in head and neck squamous cell carcinoma. Also, the predictive ability for mortality of regional lymph node metastasis can be improved with the combined evaluation of the immunohistochemical expression of these two proteins. Keywords: cyclooxygenase-2; head and neck cancer; lymphangiogenesis; metastasis; survival; vascular endothelial growth factor-C Clinical and pathological observations have shown that lymph node metastases at the time of diagnosis, is the most reliable prognostic factor for mortality or recurrence in patients with head and neck squamous cell carcinoma.

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Section: Discussionmentioning

confidence: 93%

COX-2 expression correlates with VEGF-C and lymph node metastases in patients with head and neck squamous cell carcinoma

2005

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“…Its function is unclear since it is not required for angiogenesis. However, VEGF-B expression has been detected in a wide variety of tumors such as breast carcinoma, melanoma and fibrosarcoma (24)(25)(26), neuroblastomas (27), colorectal cancer (28), oral squamous cell carcinomas (29), and often in conjunction with VEGF-A and other angiogenic factors. Moreover, its ability to activate VEGFR1 and neuropilin-1 indicates that it represents a potential anti-cancer target.…”

Section: Discussionmentioning

confidence: 99%

Expression analysis of VEGF-A and VEGF-B: Relationship with clinicopathological parameters in bladder cancer

Fauconnet¹

2009

Oncol Rep

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Abstract. The present investigation was conducted first to determine whether correlation exists between VEGF-A and -B mRNA levels and clinicopathological parameters and to assess their prognostic value in bladder cancer, then to clarify the expression level and biological significance of VEGF-A isoforms. Total RNA was isolated from 37 specimens of bladder cancer. Northern blot analysis revealed that VEGF-B mRNA was not expressed either in normal urothelium or in bladder cancer and detected three VEGF-A transcripts of 5.2, 4.5 and 1.7 kb in length, respectively. The VEGF-A transcript levels were greater in cancer tissues than in normal urothelium. They were significantly higher in pT2-T4 than in pTa and pT1 urothelial tumors and thus, were correlated to the pathologic stage. Contrary to the 4.5 kb transcript, elevated expression of the 5.2 and 1.7 kb transcripts was correlated with the histologic grade and the presence of carcinoma in situ. Patients with higher VEGF-A mRNA levels had a significantly shorter survival without progression compared to those with lower levels. Three VEGF-A splice variants were detected by Southern blotting namely, VEGF121, 165 and 189. The expression intensity of each isoform was evaluated by quantitative real-time RT-PCR in 20 new fresh frozen recent tumors. VEGF121 and VEGF165 were expressed at the similar level. On the contrary, they were significantly more expressed than VEGF189 (p<0.05). The three isoforms were higher expressed in pT2 bladder cancers than in pTa tumors (p<0.05). There was only a significant correlation between the increased expression level of VEGF121 and 165 and the histological grade of the lesion (p<0.05). To conclude, VEGF-A mRNA level is a potential prognostic indicator of progression in bladder cancer as well as the expression level of the different VEGF-A splice variants.

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“…29 The VEGF plays a decisive role in the development of blood vessels; it is a key component in tumor angiogenesis, and 4 subtypes have been described (A, B, C, and D). 43,44 Shintani et al 43 recently described its expression in OSCC, correlating subtypes A and B with tumor angiogenesis and subtypes C and D with the risk of nodal metastases. The latter were also frequently upregulated in the invasive front of the tumor, indicating a possible role in the process of tumor invasion and development of metastases.…”

Section: Review Of the Literature Patient-related Factorsmentioning

confidence: 99%

Oral squamous cell carcinoma: Review of prognostic and predictive factors

Massano

Regateiro

Januário

et al. 2006

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, an

547

436

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Expression of vascular endothelial growth factor A, B, C, and D in oral squamous cell carcinoma

Cited by 122 publications

References 26 publications

COX-2 expression correlates with VEGF-C and lymph node metastases in patients with head and neck squamous cell carcinoma

COX-2 expression correlates with VEGF-C and lymph node metastases in patients with head and neck squamous cell carcinoma

Expression analysis of VEGF-A and VEGF-B: Relationship with clinicopathological parameters in bladder cancer

Oral squamous cell carcinoma: Review of prognostic and predictive factors

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