Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma

Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma

Author Carvalho, Ana Carolina de Autor UNIFESP Google Scholar
Scapulatempo-Neto, Cristovam Google Scholar
Maia, Danielle Calheiros Campelo Autor UNIFESP Google Scholar
Evangelista, Adriane Feijo Google Scholar
Morini, Mariana Andozia Google Scholar
Carvalho, Andre Lopes Google Scholar
Vettore, Andre Luiz Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Barretos Canc Hosp
Duke NUS Grad Med Sch
Abstract Background: 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. 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.Methods: An 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.Results: Seven 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.Conclusions: the 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.
Keywords Diagnostic markers
Fine-needle aspiration biopsies
Head and neck cancers
MicroRNAs
miR-200 family
miR-203
miR-205
Neck metastases
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2012/14837-7
Date 2015-05-09
Published in Bmc Medicine. London: Biomed Central Ltd, v. 13, 14 p., 2015.
ISSN 1741-7015 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent 14
Origin http://dx.doi.org/10.1186/s12916-015-0350-3
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000354935300001
URI http://repositorio.unifesp.br/handle/11600/39097

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