A New Monoclonal Antibody, D2-40, for Detection of Lymphatic Invasion in Primary Tumors

Kahn, Harriette J.; Marks, Alexander

doi:10.1097/01.lab.0000028824.03032.ab

Cited by 368 publications

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“…This Endothelial lymphatic marker D2-40 A Arnaout-Alkarain et al confirmed our previous study that showed the presence of D2-40 þ lymph vessel invasion in breast cancer and other tumors. 34,35 The distinction between lymph vessel and vascular invasion in breast cancer has also been demonstrated using D2-40 and the vascular marker CD34. 36 Furthermore D2-40 has been shown to be the best marker for lymphatic endothelium.…”

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confidence: 98%

“…33 We observed that D2-40 identified lymph vessel invasion in paraffinembedded sections of primary carcinomas of breast, colon, prostate, cervix and endometrium as well as melanomas. 34,35 In a pilot study of 50 breast cancers, D2-40 increased the detection of lymph vessel invasion by 20% in node-negative cases and 16% in node-positive cases. 34 Van den Eynden et al's 36 study also showed that D2-40 distinguished lymphatic invasion from blood vessel invasion in breast cancers.…”

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confidence: 99%

“…34,35 In a pilot study of 50 breast cancers, D2-40 increased the detection of lymph vessel invasion by 20% in node-negative cases and 16% in node-positive cases. 34 Van den Eynden et al's 36 study also showed that D2-40 distinguished lymphatic invasion from blood vessel invasion in breast cancers. In the present study, we correlated the presence of lymph vessel invasion identified by D2-40 with the clinicopathological factors in primary node-negative breast cancers.…”

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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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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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“…Prox-1 and LYVE-1 are, respectively, a transcription factor and a hyaluronan receptor that show specificity for lymphatic endothelial cells. D2-40 was originally described as a selective monoclonal antibody to a M r 40 000 O-linked sialoglycoprotein that reacts with a fixation-resistant epitope in lymphatic endothelium (Kahn and Marks, 2002). Recently, the D2-40 antibody has been shown to specifically recognise podoplanin, a glomerular podocyte membrane protein (Schacht et al, 2005) and has been shown to be a very sensitive and specific marker for lymphatic endothelium in most tissues (Evangelou et al, 2005) and especially in breast cancer .…”

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Induction of lymphangiogenesis in and around axillary lymph node metastases of patients with breast cancer

et al. 2006

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We studied the presence of lymphangiogenesis in lymph node (LN) metastases of breast cancer. Lymph vessels were present in 52 of 61 (85.2%) metastatically involved LNs vs 26 of 104 (25.0%) uninvolved LNs (Po0.001). Furthermore, median intra-and perinodal lymphatic endothelial cell proliferation fractions were higher in metastatically involved LNs (Po0.001). This is the first report demonstrating lymphangiogenesis in LN metastases of cancer in general and breast cancer in particular. Lymph node (LN) status is the most important prognostic factor for patients with breast cancer. The presence and the extent of axillary LN metastases reflect the probability that the cancerous process has spread through the body and both are strongly correlated with the development of distant metastases and with shortened disease-free and overall survival. Lymph node metastases are more than passive tumour deposits. Metastatic tumour sites are capable of inducing a vascular stroma and can actively contribute to tumour progression and to further metastatic spread. To what extent processes involved in progression of primary tumours, such as angiogenesis and lymphangiogenesis, contribute to progression of secondary sites is largely unknown. Reports have suggested differences between primary tumours and secondary sites and between different secondary sites. Whereas primary breast tumours grow angiogenesis dependently, we demonstrated that 90% of breast cancer liver metastases grow according to an angiogenesis-independent replacement pattern (Stessels et al, 2004). The growth of breast cancer LN metastases, on the contrary, was angiogenesis dependent and angiogenesis and hypoxia in the metastases were correlated with angiogenesis and hypoxia in the primary tumours . Guidi et al (2000) demonstrated that the presence of vascular hot spots in LN metastases, but not in the primary breast tumours was associated with decreased survival.In the present study, we compared the expression of the lymphatic endothelium-specific markers Prox-1, LYVE-1 and podoplanin in metastatically involved and uninvolved LNs of patients with breast cancer. Prox-1 and LYVE-1 are, respectively, a transcription factor and a hyaluronan receptor that show specificity for lymphatic endothelial cells. D2-40 was originally described as a selective monoclonal antibody to a M r 40 000 O-linked sialoglycoprotein that reacts with a fixation-resistant epitope in lymphatic endothelium (Kahn and Marks, 2002). Recently, the D2-40 antibody has been shown to specifically recognise podoplanin, a glomerular podocyte membrane protein (Schacht et al, 2005) and has been shown to be a very sensitive and specific marker for lymphatic endothelium in most tissues (Evangelou et al, 2005) and especially in breast cancer . We investigated the presence and extent of lymphangiogenesis in LN metastases of breast cancer using the podoplanin antibody. MATERIALS AND METHODS Patients and samplesOne hundred and ten patients with operable breast cancer were included in this study, 49 patients with LN-neg...

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“…14 Several studies employed D2-40 to evaluate lymphatics in nonvascular neoplastic and nonneoplastic lesions. [15][16][17] Although the biologic significance of D2-40 immunoreactivity is unknown, it has been stated that the antibody reliably marks lymphatic but not blood vascular endothelium, [13][14][15][16][17] and postulated that staining of lesional cells in a vascular neoplasm denotes lymphothelial differentiation. 13,14 We immunostained kaposiform hemangioendotheliomas with D2-40 antibody to assess its diagnostic value and possibly elucidate the line of differentiation in this tumor.…”

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

et al. 2005

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A New Monoclonal Antibody, D2-40, for Detection of Lymphatic Invasion in Primary Tumors

Cited by 368 publications

References 6 publications

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

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

Induction of lymphangiogenesis in and around axillary lymph node metastases of patients with breast cancer

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

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