Accelerated lymphangiogenesis in malignant lymphoma: possible role of VEGF‐A and VEGF‐C

Kadowaki, Ikuko; Ichinohasama, Ryo; Harigae, Hideo; Ishizawa, Kenichi; Okitsu, Yoko; Kameoka, Junichi; Sasaki, Takeshi

doi:10.1111/j.1365-2141.2005.05695.x

Cited by 44 publications

(34 citation statements)

References 37 publications

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“…This action was found to be mediated through stimulation of VEGFR-2, a1b1 and a2b1 integrins on the surface of LECs . Certain studies have reported a significant relationship between VEGF-A expression and lymphangiogenesis in malignant lymphoma (Kadowaki et al, 2005) and in lung carcinoma (Niki et al, 2000). The current study is the first, to our knowledge, to report such a relationship in human breast cancer, in that a significant association between VEGF-A expression and high LVD was observed.…”

Section: Discussionsupporting

confidence: 63%

Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis

et al. 2007

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Vascular endothelial cell growth factors (VEGF)-A, -C and -D have potent angio and lymphangiogenic functions in experimental models, although their role in the progression of human breast cancer is unclear. The aims of the current study were to examine the relationship between the expression of the aforementioned growth factors with the angio and lymphangiogenic characteristics of breast cancer, and to assess their suitability as potential prognostic factors. Paraffin-embedded sections of 177 primary invasive breast cancer, with complete clinical follow-up information for 10 years, were stained for VEGF-A, -C, -D, podoplanin and CD34 using standard immunohistochemical approaches. The expression of the growth factors was correlated with clinicopathological criteria and patients' survival. Lymph vessel density (LVD) and microvessel density (MVD) were assessed and correlated with expression of the growth factors. Vascular endothelial cell growth factor-A, -C and -D were highly expressed in 40, 37 and 42% of specimens, respectively. High expression of VEGF-A and -C, but not of -D, was associated with a higher LVD (P ¼ 0.013 and P ¼ 0.014, respectively), a higher MVD (Po0.001 and P ¼ 0.002, respectively), the presence of lymph node metastasis (Po0.001 and Po0.001, respectively), distant metastasis (P ¼ 0.010 and P ¼ 0.008, respectively) and a shorter Overall Survival (P ¼ 0.029 and 0.028, respectively). In conclusion, breast cancers that express high levels of VEGF-A and -C are characterised by a poor prognosis, likely through the induction of angio and lymphangiogenesis. Examination of expression of VEGF-A and -C in breast cancer may be beneficial in the identification of a subset of tumours that have a higher probability of recurrence and metastatic spread.

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Section: Discussionsupporting

confidence: 63%

Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis

et al. 2007

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“…In this study, the expression of VEGF-C was also associated with LVD. This is in agreement with the results of previous studies (15,16) which estimated LVD by counting lymphatic vessels with lumen structure. In this study, we counted lymphatic vessels regardless of whether a lumen structure was observed.…”

supporting

confidence: 83%

“…Staining for VEGF-C was positive in 96% of the samples investigated in the current study. This is in agreement with the positive rates in the studies by Kadowaki et al, Pazgal et al and Ganjoo et al, which were 92.3, 100 and 98%, respectively (15,28,29). However, the VEGF-C positive rate was 36.4% in the study by Paydas et al (26).…”

supporting

confidence: 71%

Lymphangiogenesis in non-Hodgkin’s lymphoma and its correlation with cyclooxygenase-2 and vascular endothelial growth factor-C

Mei

Liu

et al. 2012

Oncology Letters

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Abstract. We aimed to investigate the correlations between lymphangiogenesis, cyclooxygenase (COX)-2 and vascular endothelial growth factor-C (VEGF-C) in non-Hodgkin's lymphoma (NHL) and their associations with the clinical parameters of patients. A total of 75 patients diagnosed with NHL were enrolled in this study. Of the 75 patients, 14 (18.7%) had low-grade and 61 (81.3%) had aggressive lymphoma. We examined the immunohistochemical expression of COX-2 and VEGF-C and estimated lymphangiogenesis by counting lymphatic vessels expressing lymph vessel endothelial hyaluronan receptor-1 (LYVE-1). Our results showed that lymphatic vessel density (LVD) was positive in 59.0% of the cases with aggressive morphology, while the LVD positive rate of indolent lymphoma was only 28.6% (P=0.039). Both COX-2 and VEGF-C were correlated with lymphangiogenesis (P=0.030 and 0.000, respectively). The expression levels of COX-2 and VEGF-C were significantly correlated (P= 0.015). LVD, COX-2 and VEGF-C were not correlated with the gender, age, lactate dehydrogenase (LDH) levels, β2 microglobulin (β2M) levels, extranodal involvement, disease stage, B symptoms or international prognostic index of the patients. In conclusion, lymphangiogenesis was correlated with aggressive histology in NHL. COX-2 and VEGF-C are inducers of lymphangiogenesis and their expression levels were correlated in NHL.

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“…The results of other studies undertaking this question are inconsistent. Some authors found lower blood vessel density in lymphomas than in reactive lymph nodes, as in the present study [13,14]. Kadowaki et al performed an MVD analysis in normal lymph nodes and in various types of lymphomas and obtained the following results: 7818 ± 3533 and 6243 ± 4027, respectively.…”

Section: Discussionmentioning

confidence: 58%

“…Kadowaki et al performed an MVD analysis in normal lymph nodes and in various types of lymphomas and obtained the following results: 7818 ± 3533 and 6243 ± 4027, respectively. On the basis of CD34 immunostain, the researchers found that angiogenesis in DLBCL in general (without division into subtypes) is less prominent than in normal lymph nodes: 3243 ± 1453 and 7818 ± 3533, respectively [14]. Korkolopoulou et al [15] and Mazur et al [16] did not observe any relationship between blood vessel density and the morphological variant of lymphoma.…”

Section: Discussionmentioning

confidence: 99%

Angiogenesis in CD5-positive Diffuse Large B Cell Lymphoma: A Morphometric Analysis

Woźnialis¹,

Gierej²,

Popławska³

et al. 2016

Adv Clin Exp Med

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type includes 3 immunohistochemical subgroups, namely germinal center B cell-like (GCB), nongerminal center B cell-like (non-GCB) and, least frequently, CD5-positive DLBCL [1].CD5-positive DLBCL remains a poorly-described, relatively new subgroup of lymphomas, constituting about 10% of DLBCL cases [1]. Sparse reports suggest worse prognosis in this populaDiffuse Large B Cell Lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. It occurs most frequently in the elderly and is typically characterized by rapid progression and thus requires immediate treatment. The current 2008 WHO classification distinguishes multiple types and variants of DLBCL, the most common of which being DLBCL, not otherwise specified (NOS). This The control group comprised 28 cases of CD5-negative DLBCL (14 females and 14 males) aged 24-82 years (mean age 58.5). The secondary control group (13 cases) consisted of normal lymphatic tissue obtained from patients without lymphoproliferative diseases. The level of angiogenesis was assessed on the basis of immunohistochemical CD34, vWF and HIF1α expression measured using morphometric methods. Results. CD5-positive DLBCL, in comparison to CD5-negative DLBCL, was characterized by: (1) higher mean of total blood vessel area, (2) higher mean total ratio of blood vessel area and staining intensity, (3) higher mean of total blood vessel area in regions defined as hot spots, (4) higher mean of total ratio of blood vessel area and staining intensity in hot spots. The measurements in lymph nodes without lymphoproliferative diseases lay between the values obtained in both DLBCL subgroups. Conclusions. We observed a significant exacerbation of angiogenesis in CD5-positive DLBCL in comparison to the CD5-negative subgroup, possibly explaining its more aggressive clinical course. Our data does not substantiate the hypothesis that angiogenesis is more pronounced in frequent CD5-negative DLBCL subgroup in comparison to benign lymphatic tissue (Adv Clin Exp Med 2016, 25, 6, 1149-1155).

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Accelerated lymphangiogenesis in malignant lymphoma: possible role of VEGF‐A and VEGF‐C

Cited by 44 publications

References 37 publications

Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis

Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis

Lymphangiogenesis in non-Hodgkin’s lymphoma and its correlation with cyclooxygenase-2 and vascular endothelial growth factor-C

Angiogenesis in CD5-positive Diffuse Large B Cell Lymphoma: A Morphometric Analysis

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