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Expressions of COX-2 and VEGF-C in gastric cancer: correlations with lymphangiogenesis and prognostic implications.

Gou HF, Chen XC, Zhu J, Jiang M, Yang Y, Cao D, Hou M - J. Exp. Clin. Cancer Res. (2011)

Bottom Line: Peritumoral LVD was significantly higher than that in both normal and intratumoral tissue (P < 0.05).VEGF-C was significantly associated with peritumoral LVD (r = 0.308, P = 0.021).Although COX-2 expression was associated with survival time, it was not correlated with VEGF-C and peritumoral LVD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center of Medical Oncology, West China Hospital, Sichuan University, PR China.

ABSTRACT

Background: Cyclooxygenase-2 (COX-2) has recently been considered to promote lymphangiogenesis by up-regulating vascular endothelial growth factor-C (VEGF-C) in breast and lung cancer. However, the impact of COX-2 on lymphangiogenesis of gastric cancer remains unclear. This study aims to test the expression of COX-2 and VEGF-C in human gastric cancer, and to analyze the correlation with lymphatic vessel density (LVD), clinicopathologic features and survival prognosis.

Methods: Using immunohistochemistry, COX-2, VEGF-C and level of LVD were analyzed in 56 R0-resected primary gastric adenocarcinomas, while paracancerous normal mucosal tissues were also collected as control from 25 concurrent patients. The relationships among COX-2 and VEGF-C expression, LVD, and clinicopathologic parameters were analyzed. The correlations of COX-2, VEGF-C and level of LVD with patient prognosis were also evaluated by univariate tests and multivariate Cox regression.

Results: The expression rates of COX-2 and VEGF-C were 69.64% and 55.36%, respectively, in gastric carcinoma. Peritumoral LVD was significantly higher than that in both normal and intratumoral tissue (P < 0.05). It was significantly correlated with lymph node metastasis and invasion depth (P = 0.003, P = 0.05). VEGF-C was significantly associated with peritumoral LVD (r = 0.308, P = 0.021). However, COX-2 was not correlated with VEGF-C (r = 0.110, P = 0.419) or LVD (r = 0.042, P = 0.758). Univariate analysis showed that survival time was impaired by higher COX-2 expression and higher peritumoral LVD. Multivariate survival analysis showed that age, COX-2 expression and peritumoral LVD were independent prognostic factors.

Conclusions: Although COX-2 expression was associated with survival time, it was not correlated with VEGF-C and peritumoral LVD. Our data did not show that overexpression of COX-2 promotes tumor lymphangiogenesis through an up-regulation of VEGF-C expression in gastric carcinoma. Age, COX-2 and peritumoral LVD were independent prognostic factors for human gastric carcinoma.

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Immunohistochemical staining of D2-40: Immunoreactivity of D2-40 proteins was found in the cytoplasm and cellular membrane of lymphatic endothelial cells. A. Detection of lymphatic vessels in the peritumoral tissue of gastric carcinoma was highlighted by immunostaining against D2-40 (LsAB,×200). B. Immunohistochemical staining of D2-40 in the intratumoral tissue of gastric carcinoma (LsAB, ×200). C. Immunohistochemical staining of D2-40 the normal gastric mucosal tissue (LsAB, ×200).
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Figure 3: Immunohistochemical staining of D2-40: Immunoreactivity of D2-40 proteins was found in the cytoplasm and cellular membrane of lymphatic endothelial cells. A. Detection of lymphatic vessels in the peritumoral tissue of gastric carcinoma was highlighted by immunostaining against D2-40 (LsAB,×200). B. Immunohistochemical staining of D2-40 in the intratumoral tissue of gastric carcinoma (LsAB, ×200). C. Immunohistochemical staining of D2-40 the normal gastric mucosal tissue (LsAB, ×200).

Mentions: Immunoreactivity of D2-40 proteins was found in the cytoplasm and cellular membrane of lymphatic endothelial cells. The distribution of D2-40-positive cells was frequently located in peritumoral tissue (hot spot) (Figure 3A). The means of LVD in peritumoral, intratumoral and normal tissue of the 56 gastric carcinomas were 9.24 ± 4.51, 2.88 ± 2.04, 2.69 ± 1.78, respectively. The LVD in peritumoral, intratumoral (Figure 3B) and normal tissue (Figure 3C) was significantly different by variance analysis of randomized block design. When compared to each other by least significant difference (LSD) test, there was a significant difference between the peritumoral LVD and both the intratumoural LVD and the LVD of normal tissue. There was no significant difference between the intratumoral LVD and the LVD of normal tissue. When the mean peritumoral LVD of 9.24 was chosen as the cut-off point for discrimination of the 56 patients, 32 patients were categorized in the low LVD group and 24 in the high LVD group.


Expressions of COX-2 and VEGF-C in gastric cancer: correlations with lymphangiogenesis and prognostic implications.

Gou HF, Chen XC, Zhu J, Jiang M, Yang Y, Cao D, Hou M - J. Exp. Clin. Cancer Res. (2011)

Immunohistochemical staining of D2-40: Immunoreactivity of D2-40 proteins was found in the cytoplasm and cellular membrane of lymphatic endothelial cells. A. Detection of lymphatic vessels in the peritumoral tissue of gastric carcinoma was highlighted by immunostaining against D2-40 (LsAB,×200). B. Immunohistochemical staining of D2-40 in the intratumoral tissue of gastric carcinoma (LsAB, ×200). C. Immunohistochemical staining of D2-40 the normal gastric mucosal tissue (LsAB, ×200).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3037339&req=5

Figure 3: Immunohistochemical staining of D2-40: Immunoreactivity of D2-40 proteins was found in the cytoplasm and cellular membrane of lymphatic endothelial cells. A. Detection of lymphatic vessels in the peritumoral tissue of gastric carcinoma was highlighted by immunostaining against D2-40 (LsAB,×200). B. Immunohistochemical staining of D2-40 in the intratumoral tissue of gastric carcinoma (LsAB, ×200). C. Immunohistochemical staining of D2-40 the normal gastric mucosal tissue (LsAB, ×200).
Mentions: Immunoreactivity of D2-40 proteins was found in the cytoplasm and cellular membrane of lymphatic endothelial cells. The distribution of D2-40-positive cells was frequently located in peritumoral tissue (hot spot) (Figure 3A). The means of LVD in peritumoral, intratumoral and normal tissue of the 56 gastric carcinomas were 9.24 ± 4.51, 2.88 ± 2.04, 2.69 ± 1.78, respectively. The LVD in peritumoral, intratumoral (Figure 3B) and normal tissue (Figure 3C) was significantly different by variance analysis of randomized block design. When compared to each other by least significant difference (LSD) test, there was a significant difference between the peritumoral LVD and both the intratumoural LVD and the LVD of normal tissue. There was no significant difference between the intratumoral LVD and the LVD of normal tissue. When the mean peritumoral LVD of 9.24 was chosen as the cut-off point for discrimination of the 56 patients, 32 patients were categorized in the low LVD group and 24 in the high LVD group.

Bottom Line: Peritumoral LVD was significantly higher than that in both normal and intratumoral tissue (P < 0.05).VEGF-C was significantly associated with peritumoral LVD (r = 0.308, P = 0.021).Although COX-2 expression was associated with survival time, it was not correlated with VEGF-C and peritumoral LVD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center of Medical Oncology, West China Hospital, Sichuan University, PR China.

ABSTRACT

Background: Cyclooxygenase-2 (COX-2) has recently been considered to promote lymphangiogenesis by up-regulating vascular endothelial growth factor-C (VEGF-C) in breast and lung cancer. However, the impact of COX-2 on lymphangiogenesis of gastric cancer remains unclear. This study aims to test the expression of COX-2 and VEGF-C in human gastric cancer, and to analyze the correlation with lymphatic vessel density (LVD), clinicopathologic features and survival prognosis.

Methods: Using immunohistochemistry, COX-2, VEGF-C and level of LVD were analyzed in 56 R0-resected primary gastric adenocarcinomas, while paracancerous normal mucosal tissues were also collected as control from 25 concurrent patients. The relationships among COX-2 and VEGF-C expression, LVD, and clinicopathologic parameters were analyzed. The correlations of COX-2, VEGF-C and level of LVD with patient prognosis were also evaluated by univariate tests and multivariate Cox regression.

Results: The expression rates of COX-2 and VEGF-C were 69.64% and 55.36%, respectively, in gastric carcinoma. Peritumoral LVD was significantly higher than that in both normal and intratumoral tissue (P < 0.05). It was significantly correlated with lymph node metastasis and invasion depth (P = 0.003, P = 0.05). VEGF-C was significantly associated with peritumoral LVD (r = 0.308, P = 0.021). However, COX-2 was not correlated with VEGF-C (r = 0.110, P = 0.419) or LVD (r = 0.042, P = 0.758). Univariate analysis showed that survival time was impaired by higher COX-2 expression and higher peritumoral LVD. Multivariate survival analysis showed that age, COX-2 expression and peritumoral LVD were independent prognostic factors.

Conclusions: Although COX-2 expression was associated with survival time, it was not correlated with VEGF-C and peritumoral LVD. Our data did not show that overexpression of COX-2 promotes tumor lymphangiogenesis through an up-regulation of VEGF-C expression in gastric carcinoma. Age, COX-2 and peritumoral LVD were independent prognostic factors for human gastric carcinoma.

Show MeSH
Related in: MedlinePlus