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. 2013 Sep 11;8(9):e75388.
doi: 10.1371/journal.pone.0075388. eCollection 2013.

Expression of angiopoietin-2 and vascular endothelial growth factor receptor-3 correlates with lymphangiogenesis and angiogenesis and affects survival of oral squamous cell carcinoma

Chao Li  1 , Jinchuan Fan, Xicheng Song, Bing Zhang, Yu Chen, Chunhua Li, Kun Mi, Hong Ma, Yufeng Song, Xiaofeng Tao, Guojun Li
Affiliations

Expression of angiopoietin-2 and vascular endothelial growth factor receptor-3 correlates with lymphangiogenesis and angiogenesis and affects survival of oral squamous cell carcinoma

Chao Li et al. PLoS One. .

Abstract

Background: Both Ang-2 and VEGFR-3 are major regulators of angiogenesis and lymphangiogenesis, respectively, and thus may affect prognosis of OSCC. We sought to determine the associations between Ang-2 and VEGFR-3 expression and survival of OSCC.

Methods: Ang-2 and VEGFR-3 expression was determined immunohistochemically in tumor tissues from 112 patients with OSCC; OSCC-adjacent noncancerous oral tissue from 85 OSCC patients; and normal oral mucosa from 37 cancer-free individuals. A log-rank test and Cox proportional hazard models were used to compare survival among different groups with expression of Ang-2 and VEGFR-3.

Results: Ang-2 and VEGFR-3 expression was upregulated in OSCC compared to nontumor tissue (all P<0.05). High Ang-2 expression positively correlated with microvessel density (MVD) (P<0.01), and high VEGFR-3 expression positively correlated with lymph node metastasis (P<0.01) and lymphatic vessel density (LVD) (P<0.01). The patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly worse survival than in patients with low expression of Ang-2 or any other co-expression status (all P<0.05), respectively. Furthermore, multivariable analysis showed that patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly increased risk of death compared with those with low expression of Ang-2 or any other co-expression status (HR, 2.7, 95% CI, 1.1-6.2 and 5.0, 1.3-15.4, respectively).

Conclusions: These results suggest that increased expression in tumors of Ang-2 may individually, or in combination with VEGFR-3, predict poor prognosis of OSCC.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Immunohistochemical expression of Ang-2 and VEGFR-3 in OSCC (streptavidin/avidin-biotin complex ×400) (A) and CD34 (scarlet; blood vessels) and D2-40 (purple-black; lymphatic vessels) in OSCC and normal oral mucosa (streptavidin/avidin-biotin comple double-labeling ×400) (B).
Figure 2
Figure 2. Rates of expression of Ang-2 and VEGFR-3 in OSCC and normal control tissues.
Figure 3
Figure 3. Correlation between Ang-2 and VEGFR-3 status with MVD (A) and LVD (B).
Figure 4
Figure 4. Kaplan-Meier survival for OSCC patients by Ang-2 (A) and VEGFR-3 (B) status.
Figure 5
Figure 5. Kaplan-Meier survival for OSCC patients by combined Ang-2 and VEGFR-3 status.
See this image and copyright information in PMC

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