Lymph vascular invasion in invasive mammary carcinomas identified by the endothelial lymphatic marker D2-40 is associated with other indicators of poor prognosis

Marinho, Vanessa Fortes Zschaber; Metze, Konradin; Sanches, Fernanda Squárcio Fernandes; Rocha, Gislene Fátima Silva; Gobbi, Helenice

doi:10.1186/1471-2407-8-64

Cited by 47 publications

(45 citation statements)

References 39 publications

(62 reference statements)

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“…Presence of lymphovascular invasion in a primary tumor has been used as an indication for the ability of this tumor to metastasis outside the breast. 1 Such tumors therefore receive more intense therapy than tumors with no lymphovascular invasion in the same disease stage. [2][3][4] The term 'lymphovascular invasion' refers to invasion of either blood vessels or lymph vessels.…”

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confidence: 99%

“…[1][2][3][4][5][6][7] In previous reports, LI was found to be independent poor prognostic factor in lymph node (LN)-negative breast cancer patients and has been recommended to be added to clinical management tools such as the 'Nottingham Prognostic Index (NPI)'. 8 However, there still remains controversy in the literature regarding the relevance of assessment of vascular invasion in LN-positive BC.…”

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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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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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“…Among known markers of lymphatic vessel endothelium, podoplanin seems to be the most promising [2]. It allows for assessment of microvessel density and demonstration of lymphovascular invasion [2][3][4][5][6][7][8][9]. However, there is no standardized method recommended for assessment of lymphangiogenesis [1].…”

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confidence: 99%

Lymphangiogenesis assessed using three methods is related to tumour grade, breast cancer subtype and expression of basal marker

Niemiec¹,

Adamczyk²,

Ambicka³

et al. 2012

pjp

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Lymphangiogenesis is a potential indicator of cancer patients' survival. However, there is no standardisation of methodologies applied to the assessment of lymphatic vessel density. In 156 invasive ductal breast cancers (T ≥ 1/N+/M0), lymphatic and blood vessels were visualised using podoplanin and CD34, respectively. Based on these markers expression, four parameters were assessed: (i) distribution of podoplanin-stained vessels (DPV) -the percentage of fields with at least one lymphatic vessel (a simple method proposed by us), (ii) lymphatic vessel density (LVD), (iii) LVD to microvessel density ratio (LVD/MVD) and (iv) the expression of podoplanin in cancer-associated fibroblasts. Next, we estimated relations between the above-mentioned parameters and: (i) breast cancer subtype, (ii) tumour grade, and (iii) basal markers expression. We found that intensive lymphangiogenesis, assessed using all studied methods, is positively related to high tumour grade, triple negative or HER2 subtype and expression of basal markers. Whereas, the absence of podoplanin expression in fibroblasts of cancer stroma is related to luminal A subtype, low tumour grade or lack of basal markers expression. Distribution of podoplanin-stained vessels, assessed by a simple method proposed by us (indicating the percentage of fields with at least one lymphatic vessel), might be used instead of the "hot-spot" method.

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“…It has been shown that D2-40 is the most sensitive and specific antibody for the detection of lymphatic endothelium in different malignancies like gastric [19], colorectal [20], vulvar [21], breast [22] and endometrial cancer [23].…”

Section: Introductionmentioning

confidence: 99%

Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin) is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer

Kozłowski¹,

Naumnik²,

Nikliński³

et al. 2011

Folia Histochem Cytobiol.

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Abstract:The discovery of markers to lymphatic endothelial cells and the development of novel antibodies to these markers have brought increasing attention to the lymphatics and progress in the understanding of lymphangiogenesis and cancer metastasis. In this study, we investigate the presence of lymphatic vessel invasion (LVI) detected by D2-40 immunohistochemical staining in resected esophageal cancer and correlated with clinicopathologic data and patient survival. Sixty nine patients, who had a primary resection of esophageal cancer, were analyzed by univariate and multivariate logistic regression, and univariate and multivariate survival analysis. The total rate of LVI was 72% (50/69). Positive LVI was significantly correlated with lymph node metastasis (p < 0.001), tumor size (p < 0.001), histological grading (p = 0.017), tumor depth (p = 0.001), and stage (p < 0.001). Multivariate logistic analysis identified LVI (p = 0.036) as a predictor of regional lymph node metastasis. On univariate survival analysis, patients with LVI had a significantly shorter disease-free survival, cancer-specific survival and overall survival. Multivariate analysis proved that LVI diagnosed by D2-40 is an independent prognostic factor of both disease-free survival (p = 0.04) and overall survival (p = 0.032) in resected esophageal cancer. These results show that LVI assessment identifies patients at high risk for regional lymph node metastasis and that LVI is an independent prognostic factor in patients with esophageal cancer. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 90-97) Key words: esophageal cancer, lymphatic vessel invasion, podoplanin, D2-40, lymph node metastasis, prognosis ageal cancer. More than 65% of patients with localized esophageal cancers and negative resection margin have a positive lymph node at the time of surgery [1]. However, despite complete tumor resection and extensive lymphadenectomy, systemic and local recurrence is common [2] and the five-year survival rate is 15-39% [3].The discovery over the last decade of markers of lymphatic endothelial cells like podoplanin (D2-40) [4], LYVE-1 [5] and Prox 1 [6], and the development of novel antibodies to these markers, have generated

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Lymph vascular invasion in invasive mammary carcinomas identified by the endothelial lymphatic marker D2-40 is associated with other indicators of poor prognosis

Cited by 47 publications

References 39 publications

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

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

Lymphangiogenesis assessed using three methods is related to tumour grade, breast cancer subtype and expression of basal marker

Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin) is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer

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