Abstract
BackgroundThe presence of metastatic disease in cervical lymph nodes of head and neck squamous cell carcinoma (HNSCC) patients is a very important determinant in therapy choice and prognosis, with great impact in overall survival. Frequently, routine lymph node staging cannot detect occult metastases and the post-surgical histologic evaluation of resected lymph nodes is not sensitive in detecting small metastatic deposits. Molecular markers based on tissue-specific microRNA expression are alternative accurate diagnostic markers. Herein, we evaluated the feasibility of using the expression of microRNAs to detect metastatic cells in formalin-fixed paraffin-embedded (FFPE) lymph nodes and in fine-needle aspiration (FNA) biopsies of HNSCC patients.MethodsAn initial screening compared the expression of 667 microRNAs in a discovery set comprised by metastatic and non-metastatic lymph nodes from HNSCC patients. The most differentially expressed microRNAs were validated by qRT-PCR in two independent cohorts: i) 48 FFPE lymph node samples, and ii) 113 FNA lymph node biopsies. The accuracy of the markers in identifying metastatic samples was assessed through the analysis of sensitivity, specificity, accuracy, negative predictive value, positive predictive value, and area under the curve values.ResultsSeven microRNAs highly expressed in metastatic lymph nodes from the discovery set were validated in FFPE lymph node samples. MiR-203 and miR-205 identified all metastatic samples, regardless of the size of the metastatic deposit. Additionally, these markers also showed high accuracy when FNA samples were examined.ConclusionsThe high accuracy of miR-203 and miR-205 warrant these microRNAs as diagnostic markers of neck metastases in HNSCC. These can be evaluated in entire lymph nodes and in FNA biopsies collected at different time-points such as pre-treatment samples, intraoperative sentinel node biopsy, and during patient follow-up. These markers can be useful in a clinical setting in the management of HNSCC patients from initial disease staging and therapy planning to patient surveillance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0350-3) contains supplementary material, which is available to authorized users.
Highlights
The presence of metastatic disease in cervical lymph nodes of head and neck squamous cell carcinoma (HNSCC) patients is a very important determinant in therapy choice and prognosis, with great impact in overall survival
To the best of our knowledge, this is the first study to demonstrate the usefulness of miR-203 and miR-205 expression as a sensitive, specific, and accurate molecular approach for the diagnosis of cervical lymph node metastases
Our results suggest that the evaluation of miR-203 and miR-205 expression could be an important tool for the management of HNSCC patients, assisting in the stratification of patients that may harbor neck metastases, aiding in therapy planning and patient surveillance, contributing to an improvement in quality of life and survival rates
Summary
The presence of metastatic disease in cervical lymph nodes of head and neck squamous cell carcinoma (HNSCC) patients is a very important determinant in therapy choice and prognosis, with great impact in overall survival. We evaluated the feasibility of using the expression of microRNAs to detect metastatic cells in formalin-fixed paraffin-embedded (FFPE) lymph nodes and in fine-needle aspiration (FNA) biopsies of HNSCC patients. Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world, with an incidence of approximately 600,000 new cases per year [1]. Besides being an important prognostic indicator, the presence of metastatic disease in lymph nodes influences the choice of the adjuvant therapy used to reduce disease recurrence [7,8,9]. Assessment of the neck has become an integral part of the treatment planning for HNSCC patients
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