Prediction of lymphatic invasion by peritumoral lymphatic vessel density in prostate biopsy cores

Kuroda, Kenji; Horiguchi, Akio; Asano, Tomohiko; Hayakawa, Masamichi

doi:10.1002/pros.20768

Cited by 19 publications

(16 citation statements)

References 22 publications

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“…We confirmed in a previous study that lymphatic parameters such as the average or maximal PTLD determined using the D2-40 antibody, which is specific for lymphatic but not vascular vessels, in positive biopsy cores were significant and independent predictors of lymphatic invasion in surgical specimens [8] , and recon- firmed in the present study the impact of the PTLD values on lymphatic invasion in surgical specimens ( table 2 ). This means that prediction of BCR on the basis of the lymphatic parameters used for biopsy tissue samples might be possible.…”

Section: Discussionsupporting

confidence: 78%

“…Because this antibody does not react with the endothelium of blood vessels, lymphatic vessels can be differentiated from blood vessels [9] . PTLD assessed by using the D2-40 antibody for immunostaining has been suggested to correlate with the lymphatic invasion in radical prostatectomy specimens and lymph node metastasis [11,12] , and we found that the PTLD values in biopsy cores were independent predictors of the lymphatic invasion in prostatectomy specimens [8] .…”

Section: Introductionmentioning

confidence: 60%

“…We speculate that PTLD parameters may be an independent predictor of BCR if lymphatic invasion is a risk factor for BCR because the PTLD values in biopsy specimens were independent prognostic factors for lymphatic invasion in surgical specimens [8] . In the present study, we reconfirmed whether the PTLD values were significantly associated with the presence of lymphatic invasion in radical prostatectomy specimens, and investigated whether the lymphatic invasion in prostatectomy specimens could be a postoperative prognostic factor for BCR, and then examined whether the PTLD parameters in biopsy specimens could work as preoperative predictors of BCR in patients with localized prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

“…In a previous study using D2-40 antibody, we examined the impact of peritumoral lymphatic vessel density (PTLD) on pathological findings of radical prostatectomy specimens [8] . Monoclonal antibody D2-40 detects a fixation-resistant epitope on podoplanin, which is a specific endothelial marker of lymphatic vessels [9,10] .…”

Section: Introductionmentioning

confidence: 99%

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Prediction of Biochemical Recurrence after Radical Prostatectomy Using Peritumoral Lymphatic Vessel Density in Biopsy Specimens in Patients with Localized Prostate Cancer

Kuroda

Horiguchi²,

Tasaki³

et al. 2012

Urol Int

Self Cite

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Introduction: Lymphatic invasion has been associated with biochemical recurrence (BCR), and many patients with postoperative elevation of prostate-specific antigen (PSA) develop distant metastases within several years. We previously found peritumoral lymphatic vessel density (PTLD) in biopsy cores to be an independent predictor of lymphatic invasion in radical prostatectomy specimens, so we speculate that PTLD parameters in biopsy specimens could also be independent predictors of BCR after surgery. Patients and Methods: We obtained positive biopsy cores from 110 patients who underwent radical prostatectomy at our institution. Biopsy cores were immunostained with the D2-40 monoclonal antibody, which specifically and selectively detects lymphatic endothelium. We evaluated differences between the BCR-free survival rates and used univariate and multivariate analyses to detect independent predictors of BCR. Results: The results of a Cox proportional hazards model showed that lymphatic invasion in prostatectomy specimens was one of the independent postoperative prognostic factors for BCR (p = 0.0338). An additional model showed that one PTLD parameter, maximal PTLD, was among the independent preoperative predictors of lower BCR-free survival rates (p = 0.0200). Conclusions: Information about PTLD in prostate biopsy specimens could be helpful for selecting patients as radical prostatectomy candidates, and patients with high PTLD values should be carefully monitored after surgery.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prediction of Biochemical Recurrence after Radical Prostatectomy Using Peritumoral Lymphatic Vessel Density in Biopsy Specimens in Patients with Localized Prostate Cancer

Kuroda

Horiguchi²,

Tasaki³

et al. 2012

Urol Int

Self Cite

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“…1,2 Many studies have shown that there is a relationship between malignant tumor metastases and increased density of intratumoral lymphatic vessels. [3][4][5][6] Most of these results come from the immunohistochemical staining of intratumoral lymphatic vessels in sections of tumor specimens, and the specific biomarkers used for lymphatic vessels are several proteins, which are expressed in lymphatic endothelial cells (LECs), such as the mucin-type transmembrane protein Podoplanin, 7 lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), 8 homeobox transcription factor Prox-1, 9 and vascular endothelial growth factor receptor-3 (VEGFR-3). [10][11][12] Although the in vitro method is the current gold standard for the study of intratumoral lymphatic vessels, the occurrence and development of lymphatic vessels cannot be dynamically observed.…”

Section: Introductionmentioning

confidence: 99%

Mouse lymphatic endothelial cell targeted probes: anti-LYVE-1 antibody-based magnetic nanoparticles

Guo¹,

Liu²,

Xu³

et al. 2013

IJN

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Purpose: To investigate the specific targeting property of lymphatic vessel endothelial hyaluronan receptor-1 binding polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (LYVE-1-PEG-USPIO) nanoparticles to mouse lymphatic endothelial cells (MLECs). Methods: A ligand specific target to lymphatic vessels was selected by immunohistochemical staining on the sections of a Lewis subcutaneous transplanted tumor. The z-average hydrodynamic diameter (HD), zeta potential, and the relaxivity of PEG-USPIO and LYVE-1-PEG-USPIO nanoparticles were determined with a laser particle analyzer and magnetic resonance T 2 spin echo sequence, respectively. Prussian blue staining and transmission electron microscopy (TEM) of nanoparticle labeled cells were performed to determine the nanoparticles' binding form. Magnetic resonance imaging (MRI) was performed in vitro to evaluate the signal enhancement on the T 2 spin echo sequence of the nanoparticle labeled cells. The iron content of the labeled cells after the Prussian blue staining and MRI scanning was determined by atomic absorption spectroscopy (AAS). Results:The anti-LYVE-1 antibody was used as the specific ligand to synthesize the target probe to the MLECs. The mean z-average HDs of the LYVE-1-PEG-USPIO and PEG-USPIO nanoparticles were 57.42 ± 0.31 nm and 47.91 ± 0.73 nm, respectively, and the mean zeta potentials of the LYVE-1-PEG-USPIO and PEG-USPIO nanoparticles were 12.38 ± 4.87 mV and 2.57 ± 0.83 mV, respectively. The relaxivities of the LYVE-1-PEG-USPIO and PEG-USPIO nanoparticles were 185.48 mM -1 s -1 and 608.32 mM -1 s -1 . Cells binding nanoparticles were visualized as blue granules in the Prussian blue staining. The TEM results of the labeled cells showed the specific localization of nanoparticles. The AAS results of labeled cells after the Prussian blue staining and MRI scanning showed that the LYVE-1-PEG-USPIO nanoparticles had good binding selectivity for MLECs. MRI results indicated that the PEG-USPIO and LYVE-1-PEG-USPIO nanoparticles could generate contrast on T 2 -weighted imaging, and the correlation between R 2 and the iron content of the labeled cells was significantly positive. Conclusion:This study demonstrated that LYVE-1-PEG-USPIO nanoparticles might potentially be used as an MRI contrast agent for targeting MLECs, and the magnetic properties of LYVE-1-PEG-USPIO nanoparticles were suitable for MRI.

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Mechanisms of lymphatic metastasis in human colorectal adenocarcinoma

Royston

Jackson

2009

The Journal of Pathology

105

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The invasion of lymphatic vessels by colorectal cancer (CRC) and its subsequent spread to draining lymph nodes is a key determinant of prognosis in this common and frequently fatal malignancy. Although tumoural lymphangiogenesis is assumed to contribute to this process, review of the current literature fails to support any notion of a simple correlation between lymphatic vessel density and CRC metastasis. Furthermore, attempts to correlate the expression of various lymphangiogenic growth factors, most notably VEGF-C and VEGF-D, with the lymphatic metastasis of CRC have provided contradictory results. Recent evidence from animal and human models of tumour metastasis suggests that complex functional and biochemical interactions between the microvasculature of tumours and other cell types within the tumour microenvironment may play a pivotal role in the behaviour of commonly metastasizing tumours. Indeed, previous insights into tumoural blood vessels have provided candidate markers of tumoural angiogenesis that are currently the subject of intense investigation as future therapeutic targets. In this review article we survey the current evidence relating lymphangiogenesis and lymphangiogenic growth factor production to metastasis by CRC, and attempt to provide some insight into the apparent discrepancies within the literature. In particular, we also discuss some new and provocative insights into the properties of tumoural lymphatics suggesting that they have specific expression profiles distinct from those of normal lymphatic vessels and that appear to promote metastasis. These findings raise the exciting prospect of future biomarkers of lymphatic metastasis and identify potential targets for new generation anti-tumour therapies.

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Prediction of lymphatic invasion by peritumoral lymphatic vessel density in prostate biopsy cores

Abstract: PTLD in prostate biopsy specimens assessed by immunohistochemistry using D2-40 antibody could be a useful parameter for predicting lymphatic spread of clinically localized prostate cancer.

Cited by 19 publications

References 22 publications

Prediction of Biochemical Recurrence after Radical Prostatectomy Using Peritumoral Lymphatic Vessel Density in Biopsy Specimens in Patients with Localized Prostate Cancer

Prediction of Biochemical Recurrence after Radical Prostatectomy Using Peritumoral Lymphatic Vessel Density in Biopsy Specimens in Patients with Localized Prostate Cancer

Mouse lymphatic endothelial cell targeted probes: anti-LYVE-1 antibody-based magnetic nanoparticles

Mechanisms of lymphatic metastasis in human colorectal adenocarcinoma

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