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

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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Biol Sci, Lab Canc Mol Biol, BR-04039032 São Paulo, SP, BrazilBarretos Canc Hosp, Mol Oncol Res Ctr, BR-14784400 Barretos, SP, BrazilBarretos Canc Hosp, Dept Pathol, BR-14784400 Barretos, SP, BrazilBarretos Canc Hosp, Dept Head & Neck Surg, BR-14784400 Barretos, SP, BrazilDuke NUS Grad Med Sch, Canc Stem Cell Biol Program, Singapore 169857, SingaporeUniversidade Federal de São Paulo, Dept Biol Sci, Lab Canc Mol Biol, BR-04039032 São Paulo, SP, BrazilFAPESP: 2012/14837-7Web of Scienc

Evaluation of the expression profile of microRNAs as prognostic markers in early laryngeal tumors treated with exclusive radiotherapy

O cancer de laringe estagio clinico inicial apresenta indices de cura acima de 80% com radioterapia exclusiva. Entretanto, quando estes tumores recorrem, a cirurgia de resgate e a principal opcao de tratamento, sendo que cerca de 50% dos casos necessitarao de laringectomia total. A identificacao de marcadores que possam predizer as chances de sucesso com a radioterapia reduzindo as recaidas tumorais e reduzindo a necessidade de resgates cirurgicos que afetam a fonacao e impactam negativamente na qualidade de vida e de suma importancia para o tratamento destes pacientes. Neste cenario, o objetivo deste estudo foi identificar microRNAs que possam segregar tumores radiorresistentes dos radiossensiveis, prognosticar os tumores pre-tratamento e predizer falha ao tratamento radioterapico exclusivo para os carcinomas de celulas escamosas estadio clinico I e II primarios de laringe. Para isto, analisamos o perfil de expressao de 667 microRNAs utilizando-se o Taqman low density array (TLDA). Desta forma, cinco microRNAs foram selecionados (miR-296, miR-452, miR-183*, miR-16*, miR-200c) com base na diferenca de expressao e revisao de literatura para terem sua expressao avaliada em amostras de carcinoma de celulas escamosas de laringe em 34 pacientes, 20 radiorresistentes e 14 radiossensiveis, por qRT-PCR. O miR-296 apresentou uma distribuicao diferencial entre os grupos radiorresistente e radiossensivel estatisticamente significante (p=0,002), tendo associando-se com radiorresistencia (p= 0,01) com um odds-ratio de 8,556 e intervalo de confianca variando entre 1,7 e 42,2BV UNIFESP: Teses e dissertaçõe

Identification of markers for the presence of lymph nodes metastasis in patients with oral squamous cell carcinomas

Universidade Federal de São Paulo, São Paulo, BrazilHosp Canc Barretos, Barretos, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Search for mutations in signaling pathways in head and neck squamous cell carcinoma

Mutations in JAK-STAT signaling pathway genes have been associated with the development of various hematological tumors, but have not been investigated in head and neck tumors, and the PIK3CA, BRAF and KRAS genes have been described in a few cases of head and neck squamous cell carcinoma (HNSCC). in the present study, we determined the mutation status in members of the MAPK, PI3K-AKT and JAK-STAT pathways in HNSCC. Mutations in the KRAS, BRAF, PIK3CA, JAK1 and JAK2 genes were evaluated in 94 HNSCCs by direct DNA sequencing analysis using cDNA synthesized from RNA extracted from patient tumor cells. All patients evaluated had wild-type KRAS, BRAF and PIK3CA genes. Furthermore, although some known polymorphisms have been found in JAK1 genes (rs45598436, rs17127063, rs2230587, rs3737139, rs2230588 and rs12129819) and JAK2 (rs10429491, rs2230723, rs2230724 and rs41316003), no mutation could be detected. Our data indicate that mutations in these kinase genes seem to be rare events in HNSCC.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fed Univ São Paulo UNIFESP, Lab Mol Canc Biol, Dept Sci Biol, BR-04039032 São Paulo, BrazilBarretos Canc Hosp, Dept Head & Neck Surg, BR-14784400 Barretos, SP, BrazilFed Univ São Paulo UNIFESP, Lab Mol Canc Biol, Dept Sci Biol, BR-04039032 São Paulo, BrazilFAPESP: 2008/58460-9CNPq: 313181/2009-8CNPq: 302360/2008-5Web of Scienc

Unequal burden of mortality from gastric cancer in Brazil and its regions, 2000-2015

Background: Gastric cancer (GC) is an important cause of morbidity and mortality worldwide. However, population-based data on GC mortality dynamics in low and middle income countries are scarce. Methods: We analyzed GC mortality in Brazil based on all GC-related deaths registered 2000-2015. Results: A total of 17,374,134 deaths were recorded, with GC identified in 214,808 (1.24%) cases203,941 (94.9%) as underlying cause, and 10,867 (5.1%) as associated cause of death. Adjusted rates for age and sex was 6.85 deaths/100,000 inhabitants [95% confidence interval (CI) 6.73-6.97]. The highest mortality rates were found in males [10.00; rate ratio (RR) 1.85; 95% CI 1.78-1.91; p<0.0001] and patients 45years of age (24.98; RR 3.79; 95% CI 3.55-4.05; p<0.0001). The South (7.56; RR 1.62; 95% CI 1.50-1.76; p<0.0001) and Southeast (7.36; RR 1.59; 95% CI 1.48-1.71; p<0.0001) regions had the highest regional rates. Spatial and spatiotemporal high-risk mortality areas in 2004-2007 were located mainly in the South, Southeast, and Central-West regions. After 2008, the Northeast region became a high-risk area, especially Ceara State. Conclusion: GC remains a significant public health problem with high mortality burden and unequal distribution in Brazilian states. The new patterns in poorer regions and the high risk in some specific populations show a clear process of epidemiological transition over time. There is a need to strengthen nationwide epidemiological monitoring, surveillance, prevention, and control for GC in the country