Intratumoral lymphatic vessel density as a predictor of progression‐free and overall survival in locally advanced laryngeal/hypopharyngeal cancer

Hurst, Newton J.; Dominello, M.M.; Dyson, Gregory; Jaratli, Hayan; Sharma, Meenu; Ahmed, Yasin; Melkane, Antoine E.; Rose, Christopher; Jacobs, John R.; Giorgadze, Tamara; Kim, Harold

doi:10.1002/hed.24011

Cited by 4 publications

(4 citation statements)

References 19 publications

(43 reference statements)

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“…While much attention is given to hematological transit of cancer cells, and most chemotherapy is delivered intravenously, metastatic spread is most often initiated through tumor-draining lymphatics to regional draining LNs before draining into and disseminating through the blood circulation. Expanded peritumoral lymphangiogenesis is frequently observed as part of cancer progression and correlates with increased LN metastasis and poorer survival [51,52], further evidencing that the lymphatics provide a highway for system dissemination. However, before cancer cells metastasize through these peritumoral lymphatics, tumor antigens (tAgs) and mature, activated dendritic cells presenting tAgs migrate through the peritumoral lymphatics to regional LNs to set up anti-tumor immune responses (Figure 1).…”

Section: The Effects Of Metastasis and Cancer Progression On Lymphatimentioning

confidence: 99%

The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors

Aldrich

Rasmussen

Fife

et al. 2020

Cancers

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Breast-cancer-acquired lymphedema is routinely diagnosed from the appearance of irreversible swelling that occurs as a result of lymphatic dysfunction. Yet in head and neck cancer survivors, lymphatic dysfunction may not always result in clinically overt swelling, but instead contribute to debilitating functional outcomes. In this review, we describe how cancer metastasis, lymph node dissection, and radiation therapy alter lymphatic function, as visualized by near-infrared fluorescence lymphatic imaging. Using custom gallium arsenide (GaAs)-intensified systems capable of detecting trace amounts of indocyanine green administered repeatedly as lymphatic contrast for longitudinal clinical imaging, we show that lymphatic dysfunction occurs with cancer progression and treatment and is an early, sub-clinical indicator of cancer-acquired lymphedema. We show that early treatment of lymphedema can restore lymphatic function in breast cancer and head and neck cancer patients and survivors. The compilation of these studies provides insights to the critical role that the lymphatics and the immune system play in the etiology of lymphedema and associated co-morbidities.

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Section: The Effects Of Metastasis and Cancer Progression On Lymphatimentioning

confidence: 99%

The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors

Aldrich

Rasmussen

Fife

et al. 2020

Cancers

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“…LN metastasis is considered a crucial prognostic factor for various cancers. 30 31 32 In a previous study, we found that high expression of VEGF-C is related to increased lymphatic vessel density (LVD) and lymphatic vessel invasion (LVI) in PCa, which could promote LN metastasis and lead to poor prognosis. 23 The significance of VEGF-C in lymphangiogenesis and LN metastasis in human malignancies has been widely recognized, 33 34 35 while TLR9 may upregulate VEGF-C by activating nuclear factor kappa B (NF-κB).…”

Section: Discussionmentioning

confidence: 99%

Coexpression of TLR9 and VEGF-C is associated with lymphatic metastasis in prostate cancer

Zeng¹,

Huang²,

Fang

et al. 2022

Asian J Androl

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Prostate cancer (PCa) is one of the most frequent cancers in men, and its biomolecular targets have been extensively studied. This study aimed to analyze the expression of toll-like receptor 9 (TLR9) and vascular endothelial growth factor C (VEGF-C) and the clinical value of the coexpression of TLR9 and VEGF-C in PCa. We retrospectively evaluated 55 patients with clinically localized, intermediate-risk, or high-risk PCa who underwent laparoscopic radical prostatectomy (LRP) and extended pelvic lymph node dissection (ePLND) without neoadjuvant hormonal therapy at a single institution from June 2013 to December 2016. In all 55 patients, the median number of lymph nodes (LNs) resected was 23 (range: 18–31), and a total of 1269 LNs were removed, of which 78 LNs were positive. Seventeen patients had positive LNs, with a positive rate of 30.9%. In addition, the immunohistochemical results in the above patients revealed that high TLR9 expression was correlated with higher Gleason score (GS) ( P = 0.049), increased LN metastasis ( P = 0.004), and more perineural invasion (PNI) ( P = 0.033). Moreover, VEGF-C expression was associated with GS ( P = 0.040), pathological stage (pT stage) ( P = 0.022), LN metastasis ( P = 0.003), and PNI ( P = 0.001). Furthermore, a significant positive correlation between TLR9 and VEGF-C was found ( P < 0.001), and the TLR9/VEGF-C phenotype was associated with LN metastasis ( P = 0.047). Collectively, we propose that TLR9 stimulation may promote LN metastasis in PCa cells through the upregulation of VEGF-C expression, thereby affecting the prognosis of PCa patients. Therefore, these markers may serve as valuable targets for the treatment of PCa.

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“…It has been demonstrated that high MVD is associated with both metastasis and poor prognosis in patients with head and neck cancers . Lymphatic vasculature has also been shown to play a role, with high LVD being associated with poor prognosis in gastric, non‐small‐cell lung, and head and neck cancers . Many of these studies have distinguished between peritumoral and intratumoral vessel densities.…”

Section: Discussionmentioning

confidence: 99%

“…9,22 Lymphatic vasculature has also been shown to play a role, with high LVD being associated with poor prognosis in gastric, non-small-cell lung, and head and neck cancers. 10,11,[23][24][25][26][27][28] Many of these studies have distinguished between peritumoral and intratumoral vessel densities. In HNSCC, high intratumoral LVD has been reported to be associated with higher risk of local recurrence, 10 cervical nodal metastases, 11,29 and worse overall survival.…”

Section: Discussionmentioning

confidence: 99%

Prognostic implications of peritumoral vasculature in head and neck cancer

et al. 2018

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BackgroundThere is conflicting evidence regarding the role of peritumoral lymphatic vessel density (LVD) and blood microvessel density (MVD) in the metastasis and prognosis of head and neck squamous cell carcinoma (HNSCC). Existing studies are limited to one or two head and neck subsites and/or small sample sizes. A larger study incorporating multiple sub‐sites is needed to address the role of peritumoral LVD and MVD in HNSCC metastasis and prognosis.MethodsTissue samples from 200 HNSCC cases were stained simultaneously using immunohistochemistry (IHC) for markers of peritumoral LVD (lymphatic vessel marker D240) and MVD (blood vessel marker CD31). Of the stained slides, 166 and 167 were evaluable for LVD and MVD, respectively. The results were then correlated with clinicopathologic features and patient outcomes.ResultsPatients with metastatic disease were more likely to have high peritumoral MVD. Through multivariable analyses, MVD was not significantly related to DFS and OS, while low LVD was related to higher risk of disease progression and poor survival.ConclusionsPeritumoral MVD was found to be positively associated with metastasis, while LVD was found to be inversely related to both metastasis and progression of HNSCC. These findings may suggest a prognostic role of both peritumoral LVD and MVD in patients with HNSCC.

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Intratumoral lymphatic vessel density as a predictor of progression‐free and overall survival in locally advanced laryngeal/hypopharyngeal cancer

Abstract: Intratumoral lymphatic vessel density is predictive of PFS and OS in locally advanced laryngeal/hypopharyngeal cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: E417-E420, 2016.

Cited by 4 publications

References 19 publications

The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors

The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors

Coexpression of TLR9 and VEGF-C is associated with lymphatic metastasis in prostate cancer

Prognostic implications of peritumoral vasculature in head and neck cancer

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