Prognostic value of lymph node ratio in head and neck squamous cell carcinoma

Talmi, Yoav P.; Takes, Robert P.; Alon, Eran E.; Nixon, Iain J.; López, Fernando; Bree, Remco de; Rodrigo, Juan P.; Shaha, Ashok R.; Halmos, György B.; Rinaldo, Alessandra; Ferlito, Alfio

doi:10.1002/hed.25080

Cited by 49 publications

(67 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 28 Tumor invasion and TNM stage are vital factors for assessment of prognosis in patients with cancer and are among the most common tools used for that purpose. 29 – 31 Our analyses revealed that DKK1 expression was higher in HNSCC patients with advanced tumor and clinical stage compared with those with early-stage disease, supporting a possible role for DKK1 in the development of HNSCC.…”

Section: Discussionmentioning

confidence: 60%

Elevated <em>DKK1</em> expression is an independent unfavorable prognostic indicator of survival in head and neck squamous cell carcinoma

Gao¹,

Li²,

Xiao³

et al. 2018

CMAR

View full text Add to dashboard Cite

PurposeDKK1 is an antagonist of the Wnt signaling pathway that has various roles in human physiology. Notably, aberrant DKK1 expression is observed in several cancers. In this retrospective study, we assessed the association between DKK1 expression levels and head and neck squamous cell carcinoma (HNSCC) and its prognostic value.Materials and methodsUsing RNA-seq data from HNSCC tumors (N=520) and adjacent normal tissue (N=44) in The Cancer Genome Atlas, we evaluated DKK1 expression levels. Additionally, we evaluated the association of DKK1 expression levels and pathophysiological features of patients with HNSCC and the value of DKK1 expression for prediction of overall survival (OS). We also explored the correlation between DKK1 expression and methylation of its promoter in HNSCC.ResultsDKK1 expression was significantly upregulated in HNSCC compared with normal tissues. Moreover, DKK1 expression was significantly associated with smoking, alcohol abuse, sex, human papillomavirus status, tumor site, tumor invasion, and pathologic stage in HNSCC patients. Kaplan–Meier curves showed that high DKK1 expression was correlated with inferior OS. In addition, univariate and multivariate analyses showed that elevated DKK1 expression was an independent prognostic factor for poor OS (HR: 1.85, 95% CI: 1.31–2.62, P<0.001). Regression analysis identified a strong negative correlation between DKK1 expression and methylation of its promoter.ConclusionThese findings support the hypothesis that elevated DKK1 expression is modulated via methylation of its promoter and indicate that DKK1 expression is a highly informative prognostic biomarker for patients with HNSCC.

show abstract

Section: Discussionmentioning

confidence: 60%

Elevated <em>DKK1</em> expression is an independent unfavorable prognostic indicator of survival in head and neck squamous cell carcinoma

Gao¹,

Li²,

Xiao³

et al. 2018

CMAR

View full text Add to dashboard Cite

show abstract

“…Human head and neck squamous cell carcinomas (SCC) typically reveal a phenotype of collective cell movement [14]. Indeed, clustered cohort-like cancer cell dissemination appears to be highly efficient in embolizing lymphatic and blood vessels, which are accepted as a major prognostic factor for head and neck SCC [15]. Nevertheless, little is known about the complexity of collective cell invasion in this cancer type and further work is required in order to fully understand the involvement of phenotypic plasticity of tumor and stromal cells in this phenomenon.…”

Section: Introductionmentioning

confidence: 99%

The Leader Position of Mesenchymal Cells Expressing N-Cadherin in the Collective Migration of Epithelial Cancer

Sáenz‐de‐Santa‐María

Celada

Chiara

2020

Cells

View full text Add to dashboard Cite

Understanding how heterogeneous cancer cell populations migrate collectively is of paramount importance to arrest metastasis. Here, we applied 3D culture-based approaches for in vitro modeling of the collective migration of squamous carcinoma cells and examine the impact of epithelial and mesenchymal cell interactions on this type of migration. We show that both mesenchymal N-cadherin-expressing cancer cells and cancer-associated fibroblasts cooperate in collective migration of epithelial cancer cells by leading their collective migration. This was consistent with the observed distribution of E-cadherin/N-cadherin in the human carcinoma tissues of head and neck. The presence of "leader" mesenchymal cancer cells or "leader" fibroblasts was significantly associated with metastasis development, recurrent disease and low overall disease survival in head and neck squamous cell carcinomas (HNSCC). In silico analysis of independent public datasets revealed that increased N-cadherin expression in the heterogeneous cancer tissues is associated with disease progression not only in HNSCC but also in other prevalent tumors, such as colorectal, breast and lung cancer. Collectively, our data highlight the importance of mesenchymal cells in collective cell migration and disease progression, findings that may have a broad significance in cancer, especially in those in which aberrant N-cadherin expression negatively impacts disease survival.

show abstract

“…On the other hand, a lower LNR may signify that few lymph nodes are positive out of the total removed and in consequence, the lower the value the higher the survival rate should be. Various potentially optimal cut-off values of LNY and LNR have been proposed in many retrospective studies and in two published systematic reviews [ 2 , 3 ], although no definitive results have been drawn yet. Elective neck dissection for cN0 oral and oropharyngeal cancer is routinely performed in many centers, considering the risk of occult metastasis.…”

Section: Introductionmentioning

confidence: 99%

“…LNY and LNR may have a predictive value which may help to drive treatment choices in specific population of patients. The majority of the evidence on this topic comes from retrospective studies or cancer database registries [ 3 ], which are undoubtedly a valid source of information but are also predisposed to biases due to the retrospective collection of information, such as patient selection and incomplete data acquisition. For this reason, a routine evaluation of the two parameters is not part of current clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of lymph node yield and lymph node ratio in patients affected by squamous cell carcinoma of the oral cavity and oropharynx: Study protocol for a prospective, multicenter, observational study

Iocca

Farcomeni

Virgilio

et al. 2019

Contemporary Clinical Trials Communications

View full text Add to dashboard Cite

BackgroundLymph node involvement is a fundamental prognostic factor in head and neck squamous cell carcinoma (SCC). Lymph node yield (LNY), which is the number of lymph nodes retrieved after neck dissection, and lymph node ratio (LNR), which is the ratio of positive lymph nodes out of the total removed, are measurable indicators that may have the potential to be used as prognostic factors. The present study is designed to define the exact role of LNY and LNR regarding the overall and specific survival of patients affected by oral cavity and oropharyngeal SCC. It has been registered on clinicaltrials.gov database (NCT03534778).MethodsThis is a multicenter study involving tertiary care referral centers in Europe and North America. Patients affected by oral cavity, HPV+ and HPV- oropharyngeal SCC undergoing neck dissection will be consecutively enrolled and followed-up for up to 5 years. Patients and disease characteristic will be properly recorded and centrally analyzed. The primary end-point is to define reliable cut off-values for LNY and LNR which may serve as prognosticators of survival. This will be achieved through the use of ROC curves. Secondary outcomes will be the Overall survival (OS), Disease Specific Survival (DSS), and Progression Free Survival Hazard Ratios (HR) at 2-, 3- and 5 years, which will be evaluated through the Kaplan-Meier method and the difference in survival attested by the log-rank test. Univariate and multivariate analysis will be performed to understand the association of various outcomes with LNY and LNR.

show abstract

Prognostic value of lymph node ratio in head and neck squamous cell carcinoma

Abstract: The LNR is reported to be of value in assessing prognosis in the patients with HNSCC. Although it is easy to calculate and could be considered in the staging of these patients, the currently available evidence in the literature does not yet provide a solid base for implementation.

Cited by 49 publications

References 35 publications

Elevated <em>DKK1</em> expression is an independent unfavorable prognostic indicator of survival in head and neck squamous cell carcinoma

Elevated <em>DKK1</em> expression is an independent unfavorable prognostic indicator of survival in head and neck squamous cell carcinoma

The Leader Position of Mesenchymal Cells Expressing N-Cadherin in the Collective Migration of Epithelial Cancer

Prognostic significance of lymph node yield and lymph node ratio in patients affected by squamous cell carcinoma of the oral cavity and oropharynx: Study protocol for a prospective, multicenter, observational study

Contact Info

Product

Resources

About