Prognostic Value of Lymphangiogenesis and Lymphovascular Invasion in Invasive Breast Cancer

Schoppmann, Sebastian F.; Bayer, G.; Aumayr, Klaus; Taucher, Susanne; Geleff, Silvana; Rudas, Margaretha; Kubista, E.; Hausmaninger, H.; Samonigg, Hellmut; Gnant, Michael; Jakesz, R.; Horvat, Reinhard

doi:10.1097/01.sla.0000133355.48672.22

Cited by 250 publications

(235 citation statements)

References 33 publications

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“…41,44 Others, however, maintain that the tumor invades new lymphatics that are formed during lymphangiogenesis within the tumor mass or at the invasive front of the tumor. 37,39 In this study, most foci of D2-40 þ lymph vessel invasion occurred at the invasive front of the tumor, indicating that metastasis could occur via pre-existing lymphatics or via newly formed lymphatics at the invasive front of the tumor.…”

Section: Discussionmentioning

confidence: 62%

“…Several studies have demonstrated the absence of lymphangiogenesis in breast cancer whereas others have reported the presence of lymphangiogenesis in breast cancer. [38][39][40][41][42][43][44] Intratumoral lymphangiogenesis, however, has been demonstrated using LYVE-1 in some other cancers such as head and neck squamous cell carcinomas. 45 The current study showed that few if any lymphatics were present within the tumor mass whereas lymphatics were present at the invasive front of the tumor as has been reported in some studies.…”

Section: Discussionmentioning

confidence: 99%

“…[39][40][41] Some researchers have postulated that the tumor invades existing lymphatics that are compressed by the tumor, since they noted very few lymphatics within the tumor mass whereas they were present at the invasive front of the tumor and furthermore the lymphatic endothelium showed no evidence of proliferative activity. 41,44 Others, however, maintain that the tumor invades new lymphatics that are formed during lymphangiogenesis within the tumor mass or at the invasive front of the tumor.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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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“…It is considered as a detrimental factor in cancer because metastatic dissemination and early lymph node metastasis are associated with a poor prognosis (Morice et al, 2003;Schoppmann et al, 2004). In contrast, the relevance of neolymphangiogenesis in diseases such as asthma or inflammatory arthritis (Zhang et al, 2007) remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Lymphangiogenesis Is Upregulated in Kidneys of Patients With Multiple Myeloma

Zimmer

Dahdal

Mühlfeld

et al. 2010

The Anatomical Record

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Neolymphangiogenesis has recently been demonstrated in transplanted kidneys as well as in chronic interstitial nephritis and IgA nephropathy. However, its significance in kidney disease remains to be defined and a systematic study of renal lymphangiogenesis is warranted. We investigated patients with multiple myeloma (MM) presenting in the great majority with acute renal insufficiency. Controls were allograft kidney donors and patients with renal insufficiency due to acute renal failure (ARF). Lymph vessel length density (LVD) was quantified immunohistochemically by means of antipodoplanin staining followed by computer-assisted stereology. The mean LVD in kidneys of patients with MM (23.19 mm À2 ) was higher when compared with allograft donors (7.42 mm À2 , P ¼ 0.0003) and patients with ARF (6.78 mm À2 , P ¼ 0.0002). The higher LVD was significantly associated with interstitial inflammation, and the newly formed lymph vessels were accompanied by diffuse and nodular interstitial infiltrates composed mainly of CD20 þ B cells and CD27 þ plasma cells. The infiltrates in patients with MM also displayed a higher expression of the B-cell chemoattractant CXCL13. These results demonstrate for the first time that lymphangiogenesis is a prominent feature in MM kidneys and that it is associated with a significant accumulation of macrophages, CD20 þ and CD27 þ B lymphocytes. Further studies should clarify whether these changes represent a beneficial or detrimental factor in the progression of the myeloma-related kidney damage. Anat Rec, 293:1497Rec, 293: -1505

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“…Lymphovascular invasion in tissue sections of tumours has been clearly documented to be a reliable prognostic variable predicting nodal metastasis and survival in breast, cervix cancer and impacts on decision making for therapy in testicular cancer (Warde et al, 1997;Morice et al, 2003;Schoppmann et al, 2004;Dinshaw et al, 2005). However, the prognostic significance of LVD in cancer is not clearcut.…”

Section: Discussionmentioning

confidence: 99%

Role of lymphangiogenesis in epithelial ovarian cancer

et al. 2006

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We investigated the significance of lymphatic count, vascular count and angiogenic growth factors using immunohistochemistry in 108 tumour specimens of epithelial ovarian cancer with antibodies to lymphatic vessel endothelial hyaluronan receptor (LYVE-1), platelet endothelial cell adhesion molecule CD31, vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) in epithelial ovarian cancer to understand the pathogenesis of metastasis in ovarian cancer. The effect of prognostic variables on progression-free and overall survival was assessed. On multivariate analysis, bulky residual disease after surgery was the best prognostic indicator (Po0.001) for progression-free and overall survival (Po0.001). Lymphatic count was statistically significant as a prognostic factor for progression-free (P ¼ 0.05) and overall survival (P ¼ 0.04). However, lymphatic count did not impact on survival curves. No correlation was found between lymphatic count and age, histological subtype, FIGO stage or residual disease. Vascular count, VEGF or TP expressions were not significant in either analysis. Lymphatic spread may be significant in aiding metastases in ovarian cancer but requires other biological factors to act in conjunction, as it does not have clearcut prognostic significance. Dissemination of ovarian cancer does not occur primarily through vascular or lymphatic routes but may occur through direct intraperitoneal spread of disease.

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Prognostic Value of Lymphangiogenesis and Lymphovascular Invasion in Invasive Breast Cancer

Cited by 250 publications

References 33 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

Lymphangiogenesis Is Upregulated in Kidneys of Patients With Multiple Myeloma

Role of lymphangiogenesis in epithelial ovarian cancer

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