Lack of lymphatic vascular specificity of vascular endothelial growth factor receptor 3 in 185 vascular tumors

Partanen, Taina A.; Alitalo, Kari; Miettinen, Markku

doi:10.1002/(sici)1097-0142(19991201)86:11<2406::aid-cncr31>3.0.co;2-e

Cited by 258 publications

(160 citation statements)

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“…Later in development, it becomes restricted to lymphatic endothelium in most tissue (24,25). It has also been found to be upregulated in the endothelial cells of tumor neovascularization (26) and is consistently expressed in lymphangiomas (25), Kaposi's sarcoma (24), and in hemangiomas and angiosarcomas (27). Our experience on angiosarcomas show VEGFR3 expression in over one-half of the cases (9 of 17), suggesting a derivation from an immature endothelial-type cell.…”

Section: Discussionmentioning

confidence: 79%

Splenic Angiosarcoma: A Clinicopathologic and Immunophenotypic Study of 28 Cases

et al. 2000

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Primary angiosarcoma of the spleen is a rare neoplasm that has not been well characterized. We describe the clinical, morphologic, and immunophenotypic findings of 28 cases of primary splenic angiosarcoma, including one case that shares features of lymphangioma/lymphangiosarcoma. The patients included 16 men and 12 women, aged 29 to 85 years, with a mean of 59 years and median of 63 years. The majority of patients (75%) complained of abdominal pain, and 25% presented with splenic rupture. The most common physical finding was splenomegaly (71%). Seventeen of 21 patients were reported to have anemia. Macroscopic examination showed splenomegaly in 85% cases. Sectioning revealed discrete lesions in 88% of cases, ranging from well-circumscribed firm nodules to poorly delineated foci of necrosis and hemorrhage associated with cystic spaces. Microscopically, the tumors were heterogenous; however, all cases demonstrated at least a focal vasoformative component lined by atypical endothelial cells. Solid sarcomatous, papillary, and epithelioid growth patterns were observed. The solid sarcomatous component resembled fibrosarcoma in two cases and malignant fibroushistiocytoma in one case. Hemorrhage, necrosis, hemosiderin, extramedullary hematopoiesis, and intracytoplasmic hyaline globules were frequently identified. A panel of immunohistochemical studies revealed that the majority of tumors were immunoreactive for at least two markers of vascular differentiation (CD34, FVIIIRAg, VEGFR3, and CD31) and at least one marker of histiocytic differentiation (CD68 and/or lysozyme). Metastases developed in 100% of patients during the course of their disease. Twenty-six patients died of disease despite aggressive therapy, whereas only two patients are alive at last follow-up, one with disease at 8 years and the other without disease at 10 years. In conclusion, primary splenic angiosarcoma is an extremely aggressive neoplasm that is almost universally fatal. The majority of splenic angiosarcomas coexpress histiocytic and endothelial markers by immunohistochemical analysis, which suggest that some tumors may originate from splenic lining cells.

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Section: Discussionmentioning

confidence: 79%

Splenic Angiosarcoma: A Clinicopathologic and Immunophenotypic Study of 28 Cases

et al. 2000

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“…Kaposiform hemangioendothelioma has also been shown to be positive for VEGFR-3, a predominantly lymphatic marker; 10 however, VEGFR-3 immunoreactivity is not exclusive for tumors of lymphatics. 9 It has also been stated that the predominant neoplastic component of kaposiform hemangioendothelioma (spindled cells) recapitulates the phenotype of blood vascular endothelium (CD31 and CD34 positive), whereas the SMA-positive glomeruloid islands located within the vascular nodules represent zones of platelet trapping and blood destruction. 5 Our D2-40 data suggest that the neoplastic component has a lymphothelial immunophenotype, and the observed differences in the staining of the periphery and the center of vascular D2-40 in kaposiform hemangioendothelioma LV Debelenko et al lobules further highlight the architectural, and probably functional distinction between these two compartments.…”

Section: D2-40 In Kaposiform Hemangioendotheliomamentioning

confidence: 99%

“…28 Furthermore, both blood vessel and lymphatic vascular tumors immunoreact with the VEGFR-3 antibody. 9 Another predominantly lymphothelial marker, LYVE-1 has been shown to stain endothelium of …”

Section: D2-40 In Kaposiform Hemangioendotheliomamentioning

confidence: 99%

“…8 The tumor is composed of irregular lobules of small malformed vascular channels with spindled cells; often there are abnormal adjacent lymphatics. 1,3,5 The lesional cells immunoreact with common endothelial markers (CD31 and CD34) as well as with antibodies against the vascular endothelial growth factor receptor-3 (VEGFR-3), 9,10 which preferentially stain lymphatic endothelium in adult tissues. 11 It has been suggested that VEGFR-3 immunopositivity indicates partial lymphatic endothelial differentiation 10 or, alternatively, vascular endothelial growth factor C production by the tumor cells that stimulates proliferation of adjacent lymphatics.…”

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D2-40 immunohistochemical analysis of pediatric vascular tumors reveals positivity in kaposiform hemangioendothelioma

et al. 2005

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“…VEGFR-3, a glycosylated tyrosine kinase cell surface receptor, has been used to stain lymph vessels but is also widely expressed in intratumoral blood vessels resulting in loss of specificity for lymphatics in tumors. 21,22 LYVE-1, a specific receptor for hyaluronan, is expressed in endothelium of lymphatics. 23 However, it is also expressed in some blood vessels of the lung and in hepatic sinusoids.…”

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Significance of lymph vessel invasion identified by the endothelial lymphatic marker D2-40 in node negative breast cancer

et al. 2007

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Monoclonal antibody D2-40, a marker of lymphatic endothelium, identifies tumor emboli in lymph vessels. The aim of the study was to assess whether D2-40 þ lymph vessel invasion (LVI) correlates with clinicopathologic factors including lymphovascular invasion (LVI) as assessed by haematoxylin and eosin-stained sections (H&E þ or H&EÀ) and to assess the prognostic significance in node-negative breast cancer. The study group consisted of 303 node-negative breast cancer patients that had a median follow-up of 7.6 years. Clinical and pathological data were retrieved from the Henrietta Banting database. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections of the primary invasive carcinoma using D2-40. Immunostaining with CD31 was performed on the discordant cases that were H&E þ /D2-40À. D2-40 þ lymph vessel invasion was detected in 82/303 (27%) cases. The foci of lymphatic invasion occurred predominantly at the invasive front of the tumor. The absence of D2-40 and CD31 in 13/17 discordant cases was suggestive of retraction artefact. D2-40 þ lymph vessel invasion correlated significantly with age (P ¼ 0.0003), tumor size (P ¼ 0.005), histological grade (P ¼ 0.0001), H&E þ (P ¼ o0.0001) and estrogen receptor status (P ¼ 0.005) but not with histological type or progesterone receptor status. Multivariate analysis revealed that D2-40 þ lymph vessel invasion was the only significant predictor of distant recurrence. There was no significant association between D2-40 status and local recurrence (P ¼ 0.752) or regional recurrence (P ¼ 0.13). Both D2-40 þ lymph vessel invasion (P ¼ 0.009) and H&E þ LVI cases (P ¼ 0.02) were associated with overall shorter survival in univariate analysis. These data indicate that D2-40 identifies lymphatic invasion in breast tumors and is a significant predictor of outcome in breast cancer.

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Lack of lymphatic vascular specificity of vascular endothelial growth factor receptor 3 in 185 vascular tumors

Cited by 258 publications

References 20 publications

Splenic Angiosarcoma: A Clinicopathologic and Immunophenotypic Study of 28 Cases

Splenic Angiosarcoma: A Clinicopathologic and Immunophenotypic Study of 28 Cases

D2-40 immunohistochemical analysis of pediatric vascular tumors reveals positivity in kaposiform hemangioendothelioma

Significance of lymph vessel invasion identified by the endothelial lymphatic marker D2-40 in node negative breast cancer

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