Increased Angiogenesis and Lymphangiogenesis in Inflammatory <b>
                     <i>versus</i>
                  </b> Noninflammatory Breast Cancer by Real-Time Reverse Transcriptase-PCR Gene Expression Quantification

Auwera, Ilse Van der; Laere, Steven J. Van; Eynden, Gert G. Van den; Benoy, Ina; Dam, Peter van; Colpaert, Cécile; Fox, Stephen B.; Turley, Helen; Harris, Adrian L.; Marck, Eric A. Van; Vermeulen, Peter B.; Dirix, Luc

doi:10.1158/1078-0432.ccr-04-0063

Cited by 206 publications

(149 citation statements)

References 24 publications

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“…As such it was of interest to examine if these lymphatics were newly formed or were pre-existing. In the study of Van der Auwera et al [20]. Ki-67-positive LECs were detected in 16 (*50%) noninflammatory and 12 (80%) inflammatory specimens whereas the study by van der Schaft et al [39] reported no proliferative LECs (10 specimen were studied).…”

Section: Discussionmentioning

confidence: 93%

“…No standard method is currently used for the assessment of the proliferation fraction of lymphatics (PF-L) in human tumours. Different approaches have been used with certain studies simply reporting the presence or absence of MIB-1 positive LEC nuclei [35], with others reporting the number of positive nuclei/100 LECs nuclei [20], and yet others counting the number of positive nuclei in three high power fields [21]. As both the proliferation fraction of the tumoural lymphatics (PF-L) and of the tumour emboli (PF-E) were to be assessed, specimens which had LVI were selected for the double IHC procedure; they were 54 specimens of which 41 specimens were characterized with high LVD.…”

Section: Assessment Of Lymphangiogenic and Angiogenic Characteristicsmentioning

confidence: 99%

“…Double immunohistochemical staining of tumour sections with a lymphatic marker such as D2-40 or LYVE-1 and a proliferative marker such as Ki-67/MIB-1, or proliferating cell nuclear antigen (PCNA), have been used to address this question however, as with the aforementioned, results are controversial [20,21].…”

Section: Introduction and Aimsmentioning

confidence: 99%

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Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications

Mohammed

Ellis

Elsheikh

et al. 2008

Breast Cancer Res Treat

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Controversy exists regarding the topography of lymph vessels in breast cancer, their usefulness as prognostic factors, relationship with angiogenesis and whether active lymphangiogenesis occurs within the tumour. A series of 177 well-characterized breast cancers, with long term follow up, were stained with D2-40, CD31 and CD34. Distribution of lymphatics and lymph vessel density (LVD) were assessed in three areas, intratumoural, peripheral and peritumoural and correlated with clinicopathological criteria and patient prognosis. Microvessel density (MVD) was assessed and correlated with LVD. Double immunohistochemical staining with D2-40 and MIB-1 was carried out to assess the proliferative status of lymphatics and of the tumour emboli within. Peritumoural lymphatics were detected in all tumours whereas peripheral and intratumoural lymphatics were detected in 86 and 41% of specimens, respectively. Tumours with higher total LVD were significantly associated with the presence of lymph node (LN) metastasis and shorter overall survival (OS). In multivariate analysis, tumour grade, LN status and the presence of lymphovascular invasion, but not LVD, were independent poor prognostic factors. No association was found between LVD and MVD. Proliferating lymphatics were detected in 29% of specimens and were significantly associated with dense inflammatory infiltrate. In conclusion, lymphatics are located primarily in the peritumoural and peripheral areas in breast cancer and seem to play an important role in disease progression by being routes for tumour dissemination. The lack of correlation between lymphangiogenic and angiogenic characteristics suggests two distinct processes and the presence of active lymphangiogenesis, albeit in a small portion of specimens, may have important therapeutic implications.Keywords Angiogenesis Á Breast cancer Á D2-40 Á Lymphangiogenesis and prognosis Introduction and aims

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Section: Discussionmentioning

confidence: 93%

Section: Assessment Of Lymphangiogenic and Angiogenic Characteristicsmentioning

confidence: 99%

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Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications

Mohammed

Ellis

Elsheikh

et al. 2008

Breast Cancer Res Treat

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“…We and others had shown that intratumoral lymphatics with tumor emboli do exist; however, most of the LI lesions are located in peritumoral vessels. 8,[29][30][31] We have also examined whether the frequency of LI per tumor tissue affects outcome in LN-positive tumors. In our previous study assessing LI in 1000 LN-negative BC, number of LI foci ranged from 1 to 79 per tumor section.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of lymphatic invasion in lymph node-positive breast carcinoma: findings from a large case series with long-term follow-up using immunohistochemical endothelial marker

et al. 2014

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The poor prognostic significance of lymphatic invasion (LI) in breast carcinoma (BC) as a whole and in lymph node (LN)-negative patients in particular has been recognized in several studies; however, its prognostic role in LN-positive patients is still questionable. Aim of the current study was to assess prognostic role of LI in LN-positive BC specimens. Sections from non-selected 557 LN-positive BC specimens were stained with antibody to podoplanin/D2-40. LI was identified and correlated with clinicopathological features and patients' outcome. Twenty-year overall survival (OS), disease-free interval (DFI), and development of distant metastasis (DM) or recurrence were known for all patients. LI was detected in 262/557 (47%) of specimens ranging from 1 to 350 lesion per tumor section. Its presence was associated with higher grade tumors (Po0.0001), negative hormonal receptors (Po0.0001), high HER-2 expression (P ¼ 0.006), and with increased number of positive LNs (P ¼ 0.019). In the whole LN-positive BC, presence of LI was a poor prognostic factor for OS, DFI, and development of DM both in univariate and in multivariate analysis. In further stratification of patients, LI was associated with poorer prognosis in patients with single positive LN and not in patients with 41 positive LN. In T1N1 stage, LI was highly associated with poor OS (P ¼ 0.002), DFI (Po0.0001), and DM (Po0.0001). In T2N1 patients, LI was associated only with poorer DFI (P ¼ 0.037) but not with death or DM. In the two former patient groups, LI lost significance in multivariate analysis. In conclusion, LI is a poor prognostic factor in LN-positive BC particularly for patients having single positive LN. LI therefore would add further prognostic significance when considered in treatment in those patients. We recommend incorporation of LI in breast carcinoma staging and in prognostic indices.

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“…Expression was assessed by grading each section on staining intensity with subjective scores ranging from 0 to 3, 0 -negative, 1 -weak, 2-moderate and 3 -strong expression as per previous published studies ( Van der Auwera et al, 2004). For VEGF, a cumulative score from the four sites of staining was calculated and stratified for analysis (0-3, 4-7, 8-12).…”

Section: Quantitative Analysis Of Lymphatic Vessel Blood Vessel Densmentioning

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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Increased Angiogenesis and Lymphangiogenesis in Inflammatory versus Noninflammatory Breast Cancer by Real-Time Reverse Transcriptase-PCR Gene Expression Quantification

Cited by 206 publications

References 24 publications

Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications

Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications

Prognostic significance of lymphatic invasion in lymph node-positive breast carcinoma: findings from a large case series with long-term follow-up using immunohistochemical endothelial marker

Role of lymphangiogenesis in epithelial ovarian cancer

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