High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer

Zhang, Song; Zhang, Dong; Gong, Mingfu; Li, Wen; Liao, Cuiwei; Li-guang, Zou

doi:10.1186/s12885-017-3338-x

Cited by 56 publications

(34 citation statements)

References 36 publications

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“…We also observed a meaningful correlation with respect to metastatic lymph node involvement between tumour size and lymphovascular invasion. This conclusion was in agreement with the study of Zhang et al [29].…”

Section: Discussionsupporting

confidence: 94%

Distribution of CXCR4 and tumour-infiltrating lymphocytes in breast cancer subtypes; their relationship with each other, axillary lymph node involvement, and other prognostic indicators

Pehlivan¹,

Sivrikoz²,

Dağ³

et al. 2018

pjp

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We have investigated the distribution of chemokine receptor 4 (CXCR4) and CD8-positive, tumour-infiltrating T lymphocytes (CD8+ TILs) in breast cancer subtypes and explored the relationship between them and the well-established conventional prognostic markers, including axillary lymph node involvement. A total of 250 breast cancer patients were included in the study. The patients were separated into luminal A+B, HER2 enriched/overexpressed (HER2+), and triplenegative, on the basis of their staining characteristics, via conventional staining methods. Immunohistochemical (IHC) staining for CXCR4 and CD8+ TILs were performed on the archival tissues from each patient. With increasing intensity of CXCR4 staining, there was a higher incidence of lymph node metastasis (p < 0.01). Similarly, there was a positive correlation between the primary tumour size, HER2+ subtype, lymphovascular invasion, and axillary lymph node involvement. Dense lymphocytic infiltration was observed in HER2+ and triple-negative patients. No correlation between CD8+ TILs in all sites and breast cancer subtypes was discovered. A reverse correlation was discovered with CD8+ TILs stained only intratumorally and CXCR4 expression. In conclusion, lymph node involvement correlates with higher CXCR4 expression in all breast cancer subtypes. Conversely, no such correlation is found with CD8+ TILs.

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Section: Discussionsupporting

confidence: 94%

Distribution of CXCR4 and tumour-infiltrating lymphocytes in breast cancer subtypes; their relationship with each other, axillary lymph node involvement, and other prognostic indicators

Pehlivan¹,

Sivrikoz²,

Dağ³

et al. 2018

pjp

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“…According the current study; significant positive correlation was found between VCAM-1 expression in breast carcinoma and tumor grade and histologic stage. These findings were consistent previous findings that demonstrated that the highest VCAM-1 expression levels were associated with moderately or poorly differentiated tumors and advanced stages of breast carcinoma [2,10]. According to our findings; increased VCAM-1 expression was significantly associated with high incidence of LVI, high rates of LNM suggesting that VCAM-1 is a potential independent prognostic factor for breast carcinoma.…”

Section: Discussionsupporting

confidence: 93%

Expression of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Invasive Ductal Carcinoma of the Breast

Ahmed

Hassanein³

et al. 2020

Sohag Medical Journal

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Background and Aim: VCAM-1 (CD106) expressed mainly on activated endothelial cells in response to pro-inflammatory cytokines. Recent evidences suggest that it is closely correlated with tumor formation, angiogenesis and cancer progression. The aim of the current study was to evaluate expression status of VCAM-1 in mammary invasive ductal carcinoma (IDC), and to correlate its expression with some known clinicopathological data. Methods: Formalin-fixed paraffin embedded tissue blocks of 58 specimens of IDC were evaluated for VCAM-1 expression by immunohistochemistry (IHC). Correlation of VCAM-1 expression with different clinicopathological data was measured statistically. Results: Up-regulation of VCAM-1 expression was frequently observed in less differentiated tumors and within advanced stages with poor Nottingham prognostic index (NPI). VCAM-1 overexpression was significantly associated with the presence of lymph node metastasis (LNM), lymphovascular invasion (LVI), and prominent lymphocytic infiltration. There was no significant association of VCAM-1 expression with patients' age, tumor laterality, tumor size, muscle or skin invasion, and presence of in situ component. Conclusion: VCAM-1 molecule could promote LVI and LNM. VCAM-1 is a potential independent prognostic factor for breast carcinoma.

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“…When breast cancer cells disseminate through the lymphatic vasculature the first lymph node reached, termed the sentinel, becomes colonised (36). The emerging lymph node metastasis is drained by de novo assembled lymphatic vessels, which perforate the neoplastic tissue (4,37,38). As soon as metastatic cancer cells intravasate these de novo lymphatics they are transported to the efferent lymphatic sinus and colonise downstream lymph nodes until they reach and infest distant organs (4).…”

Section: Discussionmentioning

confidence: 99%

12(S)-HETE induces lymph endothelial cell retraction inï¿½vitro by upregulation of SOX18

et al. 2018

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Metastasising breast cancer cells communicate with adjacent lymph endothelia, intravasate and disseminate through lymphatic routes, colonise lymph nodes and finally metastasize to distant organs. Thus, understanding and blocking intravasation may attenuate the metastatic cascade at an early step. As a trigger factor, which causes the retraction of lymph endothelial cells (LECs) and opens entry ports for tumour cell intravasation, MDA-MB231 breast cancer cells secrete the pro-metastatic arachidonic acid metabolite, 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid [12(S)-HETE]. In the current study, treatment of LECs with 12(S)-HETE upregulated the expression of the transcription factors SRY-related HMG-box 18 (SOX18) and prospero homeobox protein 1 (PROX1), which determine endothelial development. Thus, whether they have a role in LEC retraction was determined using a validated intravasation assay, small interfering RNA mediated knockdown of gene expression, and mRNA and protein expression analyses. Specific inhibition of SOX18 or PROX1 significantly attenuated in vitro intravasation of MDA-MB231 spheroids through the LEC barrier and 12(S)-HETE-triggered signals were transduced by the high and low affinity receptors, 12(S)-HETE receptor and leukotriene B4 receptor 2. In addition, the current findings indicate that there is crosstalk between SOX18 and nuclear factor κ-light-chain-enhancer of activated B cells, which was demonstrated to contribute to MDA-MB231/lymph endothelial intravasation. The present data demonstrate that the endothelial-specific and lymph endothelial-specific transcription factors SOX18 and PROX1 contribute to LEC retraction.

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High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer

Cited by 56 publications

References 36 publications

Distribution of CXCR4 and tumour-infiltrating lymphocytes in breast cancer subtypes; their relationship with each other, axillary lymph node involvement, and other prognostic indicators

Distribution of CXCR4 and tumour-infiltrating lymphocytes in breast cancer subtypes; their relationship with each other, axillary lymph node involvement, and other prognostic indicators

Expression of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Invasive Ductal Carcinoma of the Breast

12(S)-HETE induces lymph endothelial cell retraction inï¿½vitro by upregulation of SOX18

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