Intratumoral vessel density as prognostic factors in head and neck squamous cell carcinoma: A meta‐analysis of literature

Yu, Min; Liu, Lei; Liang, Chunshui; Li, Ping; Ma, Xuelei; Zhang, Qiongwen; Wei, Yuquan

doi:10.1002/hed.23301

Cited by 24 publications

(28 citation statements)

References 54 publications

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“…They demonstrated a correlation between tumor size and the higher MVD/CD105 ratio in oral cancers [14]. Based on this and similar studies, the concept emerged that the high MVD/CD105 values are associated with the presence of lymph node metastasis and poorer 5-year survival [15–19]. This and other studies [20] suggested that CD105 expression might serve as an important prognostic factor in HNSCC, enabling the identification of patients at high risk of recurrence and shorter survival.…”

Section: Discussionmentioning

confidence: 97%

Microvessel density in head and neck squamous cell carcinoma

Szafarowski

Sierdziński

Szczepański

et al. 2018

Eur Arch Otorhinolaryngol

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PurposeMicrovessel density (MVD) corresponds to the intensity of neo-angiogenesis. MVD assessments are based on the expression levels of the vascular endothelium markers such as, e.g., CD34 or CD105. The goal of this study was to assess MVD among patients with head and neck squamous cell carcinoma (HNSCC), and to evaluate the predictive value of MVD in head and neck cancers.MethodsThe study included 49 patients treated for HNSCC and 11 patients with dysplasia of the upper respiratory tract epithelium. Control tissues consisted of 12 normal mucous membranes of the throat. Expression levels of MVD markers were assessed by immunohistochemistry (IHC) using tissue microarrays (TMA). Clinicopathological factors and patients’ survival over the 5-year follow-up period were analyzed.ResultsThe MVD/CD34 values were found to be significantly elevated in the HNSCCs compared to the non-malignant control tissues (p = 0.001) and to dysplastic tissues. (p = 0.02). Significantly higher MVD/CD105 values were also seen in the tumor compared to the control tissues (p = 0.001) or the dysplastic tissues (p = 0.001). Unexpectedly, significantly lower MVD/CD34 values were seen in the tumor tissues of patients with the T3–T4 tumors compared to those with T1–T2 tumors (p = 0.01).ConclusionsHNSCCs have statistically higher MVD values compared to dysplasia of the upper respiratory tract epithelium. However, the MVD/CD34 values did not correlate with local invasiveness (the T feature) of HNSCCs. This counterintuitive observation suggests that assessments of MVD as performed on TMA by IHC using anti-CD34 or anti-CD105 antibodies considered to be specific for endothelial cell markers might underestimate the extent of the tumor vascularity in HNSCC.

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Section: Discussionmentioning

confidence: 97%

Microvessel density in head and neck squamous cell carcinoma

Szafarowski

Sierdziński

Szczepański

et al. 2018

Eur Arch Otorhinolaryngol

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“…S4B] and are thus considered relevant to the disease. Lymph-angiogenesis is significant clinically for many types of cancers but most appealing in head and neck cancer because lymph node metastasis is the most important clinical parameter for this malignancy (33). We found reduced lymph vessel density in Hpa2 tumors combining with a comparable decrease in VEGF-C expression (Fig.…”

Section: Discussionmentioning

confidence: 99%

Heparanase 2 Attenuates Head and Neck Tumor Vascularity and Growth

et al. 2016

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The endoglycosidase heparanase specifically cleaves the heparan sulfate (HS) side chains on proteoglycans, an activity that has been implicated strongly in tumor metastasis and angiogenesis. Heparanase-2 (Hpa2) is a close homolog of heparanase that lacks intrinsic HS-degrading activity but retains the capacity to bind HS with high affinity. In head and neck cancer patients, Hpa2 expression was markedly elevated, correlating with prolonged time to disease recurrence and inversely correlating with tumor cell dissemination to regional lymph nodes, suggesting that Hpa2 functions as a tumor suppressor. The molecular mechanism associated with favorable prognosis following Hpa2 induction is unclear. Here we provide evidence that Hpa2 overexpression in head and neck cancer cells markedly reduces tumor growth. Restrained tumor growth was associated with a prominent decrease in tumor vascularity (blood and lymph vessels), likely due to reduced Id1 expression, a transcription factor highly implicated in VEGF-A and VEGF-C gene regulation. We also noted that tumors produced by Hpa2 overexpressing cells are abundantly decorated with stromal cells and collagen deposition, correlating with a marked increase in lysyl oxidase expression. Notably, heparanase enzymatic activity was unimpaired in cells overexpressing Hpa2, suggesting that reduced tumor growth is not caused by heparanase regulation. Moreover, growth of tumor xenografts by Hpa2-overexpressing cells was unaffected by administration of a monoclonal antibody that targets the heparin binding domain of Hpa2, implying that Hpa2 function does not rely on heparanase or heparin sulfate

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“…Therefore, lymphatic vessel density (LVD) is expected to be an important factor, which determinates patients' survival (23). In spite of the discrepancies in the results of studies on the prognostic significance of LVD in breast cancer patients (9,10), the current meta-analyses demonstrated that, this parameter could be of prognostic significance in patients with breast (24), colorectal (25), head and neck cancers (26) as well as in melanoma (27). However, the authors of the aforementioned studies stress that the standardization of the LVD assessment and the future confirmatory studies on its prognostic/predictive role, are necessary.…”

Section: Introductionmentioning

confidence: 63%

Distribution of Podoplanin-Positive Tumor Vessels Predicts Disease-Specific Survival of Node-Positive Breast Cancer Patients Treated with Anthracyclines and/or Taxanes

Niemiec¹,

Adamczyk²,

Ambicka³

et al. 2014

Cancer Investigation

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We analyzed survival of 102 invasive ductal, node positive breast cancer patients, treated with surgery and adjuvant chemotherapy (anthracyclines and/or taxanes) with relation to: (a) well-known clinicopathological parameters, (b) MIB-1 labeling index (LI), (c) the distribution of podoplanin-positive vessels (DPV), expression of: (d) basal markers, and (e) fascin. Lower progression risk was found for patients with tumors characterized by (i) pN1 + pN2, (ii) MIB-1LI ≤ 28%, (iii) lack of lymphatic vessels or high tumor DPV than for patients with pN3, MIB-1LI > 28%, low DPV, respectively. Cox multivariate analysis revealed that both pN3 and low DPV were negative prognostic indicators.

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Intratumoral vessel density as prognostic factors in head and neck squamous cell carcinoma: A meta‐analysis of literature

Abstract: High counts of LVD, not MVD, are associated with worse 5-year overall survival (OS) in patients with HNSCC.

Cited by 24 publications

References 54 publications

Microvessel density in head and neck squamous cell carcinoma

Microvessel density in head and neck squamous cell carcinoma

Heparanase 2 Attenuates Head and Neck Tumor Vascularity and Growth

Distribution of Podoplanin-Positive Tumor Vessels Predicts Disease-Specific Survival of Node-Positive Breast Cancer Patients Treated with Anthracyclines and/or Taxanes

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