Impact of Vascular Endothelial Growth Factor-C and -D Expression in Human Pancreatic Cancer

Kurahara, Hiroshi; Takao, Sonshin; Maemura, Kousei; Shinchi, Hiroyuki; Natsugoe, Shoji; Aikou, Takashi

doi:10.1158/1078-0432.ccr-04-0379

Cited by 96 publications

(78 citation statements)

References 29 publications

(30 reference statements)

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“…It is noteworthy that lymph node metastasis and lymphatic invasion are correlated with CD133 expression, as a recent study demonstrated that a melanoma cell line highly enriched with CD133-expressing cells concomitantly expresses lymphoangiogenic markers, vascular endothelial growth factor receptor (VEGFR)-3 and lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 (Monzani et al, 2007). As possible correlation between VEGF-C expression and lymphangiogenesis has previously been described (Kurahara et al, 2004;Mohammed et al, 2007), we examined VEGF-C expression in pancreatic cancer specimens and found it to be significantly associated with CD133 expression (Table 2). This suggests that CD133-positive pancreatic carcinoma cells promote lymphatic metastasis not only by inducing lymphangiogenesis, but also by facilitating self-entry into the lymphatic system.…”

Section: Discussionmentioning

confidence: 91%

CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer

et al. 2008

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Although CD133 has been shown to be a marker for cancer stem cells in various tumours, its expression in pancreatic cancer has not yet been clinically reported. In this study, we investigated the relationship between CD133 expression and clinicopathological factors in pancreatic cancer. Pancreatic head carcinoma specimens from 80 patients who underwent surgical resection were immunohistochemically assessed for CD133, vascular endothelial growth factor (VEGF)-C, CXCR4, CD34, Ki-67, and cytokeratin (CK) expressions. Sixty percentage (48/80) of specimens were CD133-positive, with less than 15% cells per specimen expressing the marker. CD133-positive cells were found at the peripheral site of adenocarcinoma glandular structures and were negative for CK. There was a significant correlation between CD133 expression and clinicopathological factors, including histological type, lymphatic invasion, and lymph node metastasis (P ¼ 0.0215, 0.0023, and 0.0024, respectively). Vascular endothelial growth factor-C expression was also significantly correlated with CD133 expression (P ¼ 0.0002). Consequently, the 5-year survival rate of CD133-positive patients was significantly lower than that of CD133-negative patients (P ¼ 0.0002) and multivariate analysis revealed that CD133 expression was an independent prognostic factor (P ¼ 0.0103). These results suggest that CD133 expression in pancreatic cancer was significantly associated with lymphatic metastasis, VEGF-C expression, and prognosis.

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Section: Discussionmentioning

confidence: 91%

CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer

et al. 2008

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“…23,24 However, Clarijs et al, 25 reported newly formed lymph vessels within the solid tumors using double staining with CD31 and PAL-E. Others have recently observed intratumoral lymphatics in melanomas, 26,27 breast, 28 head and neck, 29,30 pancreatic carcinoma, 31 and islet cell tumor. 32 A recent study detected intratumoral lymphatics in 91% of colorectal carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Lymphatic microvessel density as prognostic marker in colorectal cancer

et al. 2006

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Lymph node metastases is an important prognostic indicator for disease progression and crucial for therapeutic strategies in the work-up of colorectal carcinoma. In this study, we investigated tumor lymphangiogenesis and vascular endothelial growth factor (VEGF) expression as predictive markers for the risk of lymph node metastasis and their relation to other prognostic parameters in colorectal carcinoma. Resected colorectal carcinomas from 90 patients were examined, including 30 patients without lymph node metastases, 30 with only lymph node metastases, and 30 with liver metastases. Cases were immunostained for CD31, D2-40, and VEGF. Positivity stained microvessels were counted in densely vascular/lymphatic foci (hot spots) at Â 400 field ( ¼ 0.17 mm 2 ). Intensity of staining for VEGF was scored on a two-tiered scale. D2-40 lymphatic microvessel density demonstrated significant correlation with CD31 counts (2079 vs 1876/0.17 mm 2 field, Po0.05) and VEGF expression (Po0.01). VEGF was expressed in 61/90 (67%) cases. D2-40 identified lymphatic tumor invasion in 48/90 patients, which was greater than CD31 (37/90) and hematoxylin and eosin (H&E) (31/90). There was a positive significant correlation of D2-40, CD31 counts, and VEGF expression with the presence of lymphovascular invasion and lymph node metastases (Po0.05). D2-40 lymphatic microvessel density correlated significantly with depth of invasion (pT), positive vascular pedicle lymph nodes and liver metastases (Po0.05). In conclusion, D2-40 lymphatic microvessel density showed prognostic significance with positive correlation with lymphovascular invasion, pT, and metastases to lymph nodes and liver. Immunostaining with D2-40 enhances the detection of lymphatic invasion relative to H&E staining and the endothelial marker, CD31.

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“…In accordance with the institutional guidelines of our hospital, tissue specimens were collected after delivery of informed consent (Kurahara et al, 2004).…”

Section: Methodsmentioning

confidence: 99%

Clinical significance of midkine expression in pancreatic head carcinoma

et al. 2007

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Midkine (MK) is a heparin-binding growth factor and a product of a retinoic acid-responsive gene. Midkine is overexpressed in many carcinomas and thought to play an important role in carcinogenesis. However, no studies have been focussed on the role of MK in pancreatic carcinoma. This study sought to evaluate the clinical significance of MK expression in pancreatic head carcinoma, including the relationship between immunohistochemical expression and clinicopathologic factors such as prognosis. Immunohistochemical expression of MK and CD34 was evaluated in pancreatic head carcinoma specimens from 75 patients who underwent surgical resection. Midkine was expressed in 53.3% of patients. Midkine expression was significantly correlated with venous invasion, microvessel density, and liver metastasis (P ¼ 0.0063, 0.0025, and 0.0153, respectively). The 5-year survival rate was significantly lower for patients positive for MK vs patients negative for MK (P ¼ 0.0073). Multivariate analysis revealed that MK expression was an independent prognostic factor (P ¼ 0.0033). This is the first report of an association between MK expression and pancreatic head carcinoma. Midkine may play an important role in the progression of pancreatic head carcinoma, and evaluation of MK expression is useful for predicting malignant properties of pancreatic head carcinoma.

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Impact of Vascular Endothelial Growth Factor-C and -D Expression in Human Pancreatic Cancer

Cited by 96 publications

References 29 publications

CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer

CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer

Lymphatic microvessel density as prognostic marker in colorectal cancer

Clinical significance of midkine expression in pancreatic head carcinoma

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