Câncer e desenvolvimento embrionário possuem diversos aspectos em comum, pois ambos exibem alternância entre proliferação e diferenciação celular. A família dos genes homeobox codifica fatores de transcrição fundamentais para o adequado desenvolvimento embrionário, e têm sido descritos em diferentes neoplasias. O PMX1 (Paired Mesoderm Homeobox 1) é um gene homeobox que está expresso durante o desenvolvimento de diversos tecidos mesenquimais, como o sistema cardiovascular e elementos do esqueleto. A relação entre o PMX1 e neoplasias malignas ainda não está bem estabelecida. O objetivo desse trabalho foi verificar a presença dos transcritos do gene PMX1 em carcinomas epidermóides de boca e tecidos não tumorais adjacentes. Foi realizada hibridização in situ com sondas marcadas com digoxigenina em dezesseis amostras de carcinoma epidemóide de boca e dez de tecido não tumoral adjacente. No tecido não tumoral adjacente o sinal de hibridização é mais intenso nas camadas basal e suprabasal, mesmo quando ele pode ser observado em outras camadas. No carcinoma epidermóide de boca, o sinal está disperso por todo o tecido sendo mais intenso em áreas com células isoladas. Nossos resultados mostram a presença dos transcritos do PMX1 em epitélio de boca e em carcinoma epidermóide de boca e sugerem a participação do gene PMX1 na carcinogênese de boca. A sua expressão em neoplasias pouco diferenciadas deve ser melhor analisada / Cancer and development share common features since both processes exhibit shifts between cell proliferation and differentiation. Homeobox gene family encodes transcription factors essentials for appropriate embryonic development and they have been described in different types of neoplastic tissues. PMX1 (Paired Mesoderm Homeobox 1) is homeobox gene that has been related with mesenchyma throughout development such cardiovascular system and skeletal elements, however its relation with tumor development is not well established yet. The purpose of this study was to verify the presence of PMX1 transcripts in oral squamous cell carcinomas and adjacent non-tumoral tissues. In situ hybridization was performed with probes labeled with digoxigenin in sixteen samples of squamous cell carcinoma and ten o adjacent non-tumoral tissues. In the adjacent non-tumoral tissues in situ hybridization signaling detected were more intense in the basal and parabasal layers even when it could be observed in other layers. In the oral squamous cell carcinoma the signaling was spread all over the tissue becoming more intense in areas with isolated carcinoma cells. Our findings show PMX1 transcripts in adjacent non-tumoral tissues and oral squamous cell carcinoma and suggest participation of PMX1 in oral carcinogenesis. Its expression in poorly differentiated carcinomas needs to be analyzed in detail

A busca de marcadores moleculares para o refinamento diagnóstico, classificação e estabelecimento do prognóstico dos tumores, e individualização terapêutica tem sido foco de várias pesquisas. O presente estudo teve como objetivo investigar, em carcinoma epidermóide de língua e/ou assoalho bucal, a presença de transcritos dos genes homeobox que pudessem se revelar marcadores moleculares de prognóstico e/ou agressividade tumoral. Após análise por microarray utilizando-se amostras de tumores e margens classificados como mais e menos agressivos, os genes homeobox HOXC13, HOXD10, HOXD11, IRX4, PROX1 e ZHX1 foram selecionados e sua hiper-expressão foi parcialmente validada por qRT-PCR. Observou-se aumento da expressão de HOXD10, HOXD11 e IRX4 em tumores com relação às margens correspondentes, bem como nos tumores menos agressivos em relação às suas respectivas margens. Por outro lado, os genes PROX1 e ZHX1 estavam mais expressos nas margens que nos tumores correspondentes. Esses resultados sugerem que a expressão alterada de HOXD10, HOXD11 e IRX4 pode participar no desenvolvimento do carcinoma epidermóide de língua e/ou assoalho bucal, enquanto os genes PROX1 e ZHX1 provavelmente exibem perda de função ou estão silenciados na neoplasia. Houve uma tendência de associação entre a expressão elevada de HOXD11 e presença de infiltrações linfática e perineural, e grau moderado de diferenciação da neoplasia, bem como entre a expressão elevada de HOXD10 e infiltração linfática. O gene IXR4 foi relacionado com um menor tempo de sobrevida global. Não foi possível estabelecer, dentre os genes homeobox validados por qRT-PCR, um gene ou uma combinação deles que pudesse(m) ser utilizado(s) como marcador(es) de agressividade tumoral. / The search for molecular markers to diagnosis improvement, treatment individualization and establishment of oral squamous cell carcinoma prognosis has been the focus of several studies. The present study investigated the presence of specific transcript of homeobox genes in squamous cell carcinoma of the tongue and/or floor of the mouth that might reflect relevant molecular markers of prognosis and/or tumor aggressiveness. After microarray analysis of tumor samples classified as more or less aggressive, and non tumoral margins, HOXC13, HOXD10, HOXD11, IRX4, PROX1 and ZHX1 selected and partially validated by qRT-PCR. Increased expression of HOXD10, HOXD11, IRX4 in tumors in comparison to margins as well as in less aggressive tumors related to their margins was observed. On the other hand, a decreased expression of PROX1 and ZHX1 was observed in margins compared to their respective tumors. These results suggest that the altered expression of HOXD10, HOXD11 and IRX4 may participate in the development of squamous cell carcinoma of the tongue and/or floor of the mouth, while PROX1 and ZHX1 probably present loss of function or are silenced in tumors. A tendency of association between increased expression of HOXD11 and lymphatic and perineural infiltration, as well as moderately differentiated tumors, and increased expression of HOXD10 and lymphatic infiltration was observed. Still, increased expression of IRX4 may apparently influence global survival rate. However, the results of the present study must be confirmed in a greater number of samples, and complemented with the evaluation of HOXD10, HOXD11, IRX4 protein levels. It was not possible to establish, among homeobox genes validated through qRT-PCR, a gene or a combination of genes capable of predicting tumor aggressiveness.

O carcinoma epidermóide representa mais de 90% das neoplasias malignas de cabeça e de pescoço, apresentando taxas elevadas de morbi-mortalidade. Proteínas relacionadas à invasão e proliferação celular estão em evidência devido ao seu envolvimento na carcinogênese, a exemplo da vimentina, encontrada em células de origem mesodérmica. Sua presença em células epiteliais neoplásicas contribui na transição epitélio mesenquimal e está associada à tumorigênese, à invasão celular e à metástase. O propósito deste estudo foi analisar através de métodos qualitativos (imunofluorescência e imunoistoquímica) e quantitativos (Western Blot) a expressão da vimentina em linhagens celulares de carcinoma epidermóide de cabeça e de pescoço (CECP) e em uma linhagem de queratinócitos imortalizados (HaCat) submetidas ao cultivo tridimensional em Matrigel®. O grupo controle foi representado pelas mesmas linhagens cultivadas na ausência de Matrigel®. A Vimentina apresentou marcação citoplasmática em algumas células das linhagens estudadas, exceto na HaCat, com evidente diminuição da sua expressão quando submetida ao cultivo com Matrigel®. Esses resultados foram confirmados por Western Blot. A expressão da Vimentina em diferentes linhagens de CECP pode variar dependendo da linhagem analisada, da reação de suas células aos componentes da matriz extracelular e da técnica utilizada para avaliação da expressão da proteína. / Head and neck squamous cell carcinoma (HNSCC) represents more than 90% of all head and neck malignancies, causing more deaths than any other oral disease. Proteins related to cancer growth, invasion and metastasis are in evidence due to their involvement in carcinogens, such as vimentin. This protein is observed in mesenquimal cells, however, it is considered a common finding in cervix, breast and bladder tumours. Thus its presencence in epithelial neoplasic cells contributes to epithelial-mesenchymal transition associated with tumorigenesis and tumor progression. The aim of this study was to analyse through Western Blot, Immunohistochemistry and Immunofluorescence methods, the expression of Vimentin in three different HNSCC cell lines and HaCat cell line (immortalized keratinocytes) submitted to a 3D assay into Matrigel®. The control group was represented by the same cell lines, without any treatment. Results showed that Vimentin had citoplasmatic staining in some cell of lines studied, except for HaCat cells, with evident decrease in its expression when submitted to cultive into Matrigel®. These findings were confirmed by Western Blot. Taking these results together, we conclude that in squamous cell carcinoma, the Vimentin is related to the process of tumour invasion and metastasis. This fact was showed by the reduction of its expression after treatment with Matrigel®. Therefore, the expression of Vimentin in different cell lines of HNSCC may vary according to the stimulus and, fundamentally, the localization of the tumor and the individual characteristics of neoplasic cells.

Diversas alterações genéticas estão associadas à patogênese do carcinoma epidermoide (CE), neoplasia maligna mais comum de cabeça e pescoço. Algumas dessas alterações comprometem proteínas pertencentes à via de sinalização do Akt, envolvida em diferentes fenômenos celulares. Este trabalho teve como objetivo estudar a expressão da proteína pAkt em linhagens celulares de carcinomas epidermoides de cabeça e pescoço, de forma a verificar possíveis alterações na transcrição dessa molécula em células de CE tratadas com Curcumina. Foram utilizadas duas linhagens celulares de CE de cabeça e pescoço (FaDu e SCC9) e uma linhagem de queratinócitos normais (HaCat) divididas em dois grupos: a. Grupo controle não tratado; b. Células tratadas com Curcumina. A proliferação celular foi monitorada através do teste de viabilidade celular e a análise da expressão de proteína foi realizada através da técnica do Western Blotting que revelou supressão do pAkt na linhagem celular SCC9 nos tempos de 24 e 48 horas. Desta forma, conclui-se que a Curcumina na via do Akt em carcinomas epidermoides de cabeça e pescoço tem importante ação supressora do gene pAkt. / Several genetic alterations are associated with the pathogenesis of squamous cell carcinoma (SCC), the most common malignant neoplasm of the head and neck. Some of these changes compromise the proteins belonging to the Akt signaling pathway, involved in various cellular phenomena. The objective of this study to explores the expression of the pAkt protein in cell lines of the squamous cell carcinomas of the head and neck to verify possible changes in the transcription of this molecule in EC cells treated with curcumin. The study used two cell lines of EC head and neck (FaDu and SCC9) and a normal line of keratinocytes (HaCat), split into two groups: A. the controlled group, untreated; B. Cells treated with curcumin. The cell proliferation it was observed by cell viability test and analysis of protein expression performed through Western blotting technique revealed suppression of pAkt in SCC9 cell line at 24 and 48 hours. Thus, it is concluded that the Curcumin on the path of Akt in squamous cell carcinoma of the head and neck has a significant suppressive effect of gene Akt.

O câncer de cavidade oral é uma das neoplasias mais comuns no Brasil e no mundo, porém seu prognóstico ainda é incerto principalmente devido ao diagnóstico tardio e presença de metástases. A análise de fatores relacionados ao prognóstico dessa doença é de suma importância e, o receptor de quimiocina denominado CXCR4, está sendo relacionado a um pior prognóstico devido a maior capacidade de invasão das células que o expressam, em diversas neoplasias. Apesar dessa relação estar demonstrada em vários tipos de cânceres, com relação ao de cavidade oral pouco se sabe até o momento. Assim, objetivo desse trabalho foi analisar a expressão imuno-histoquímica do receptor de quimiocina CXCR4 em carcinomas epidermóides de cavidade oral, e relacioná-la com variáveis clínicas e histológicas. Foram obtidos 94 blocos de carcinomas epidermóides oriundos de instituições parceiras para obtenção de cortes histológicos convencionais, corados com hematoxilina e eosina (HE), e cortes de TMA (tissue microarray). Foi realizado imuno-histoquímica para anticorpo anti-CXCR4 (ab124824, ABCAM, EUA) e análise da marcação em lâminas de TMA utilizando o software Image J (versão 1.49u). A intensidade de marcação imuno-histoquímica foi correlacionada com dados clínicos (TNM, tabagismo, etilismo e sobrevida) e histopatológicos (diferenciação histológica, infiltrado inflamatório e infiltração vascular, linfática e perineural) dos pacientes. Dos casos analisados 74,4% exibiram uma marcação fortemente positiva para o CXCR4, enquanto que o epitélio não tumoral mostrou uma marcação negativa ou fracamente positiva (71,1%; p=0,011). Tumores classificados como \"bem diferenciados\" apresentaram marcação fortemente positiva para a proteína estudada (53,3%; p=0,049). Não houve associação entre a marcação imuno-histoquímica do CXCR4 com sobrevida global em 5 anos (?2= 0.3, p=0.565). Os resultados sugerem que a alta expressão dessa proteína não influencia no prognóstico e na sobrevida desses pacientes. / Oral cancer is one of the most common neoplasia in Brazil and the world. Mainly due to a late diagnosis and presence of metastases its prognosis is still uncertain. Finding biological markers related to the prognosis of this disease is of paramount importance. The chemokine receptor CXCR4 is being related to a worse prognosis in several neoplasms because cells expressing it acquire a greater capacity of invasion. Although this relationship is demonstrated in several types of cancers, in the oral cavity it is uncertain. The aim of this study was to analyze by immunohistochemistry the CXCR4 chemokine receptor expression in oral squamous cell carcinomas, and related to clinical and histological variables. Conventional histological sections stained with hematoxylin and eosin (HE) were acquired from 94 blocks of oral squamous cell carcinoma for histological analysis. TMA (tissue microarray) was assembled from these blocks for anti-CXCR4 immunohistochemistry (ab124824, ABCAM, USA). Staining analysis was performed using Image J software (version 1.49u). The immunohistochemical signal intensity was correlated with clinical (TNM, smoking, alcoholism and survival) and histopathological parameters (histological differentiation, inflammatory infiltration, vascular, lymphatic and perineural infiltration). From the cases studied 74.4% showed a strong positivity for CXCR4, and the non-tumoral epithelium was negative or weakly positive (71.1%; p = 0.011). Tumors histologically well differentiated were strongly positive for the protein studied (53.3%; p = 0.049). There was no association between CXCR4 signal and global survival in 5 years (?2= 0.3, p=0.565). These results suggest that a high expression of CXCR4 it is not related to prognosis and survival of patients of patients with oral squamous cell carcinoma.

Oncolytic viruses can be genetically modified to limit their replication in normal cells rendering them a cancer specific treatment. In addition, they can induce a 'danger signal' in the form of pathogen- and damage-associated molecular patterns leading to anti-tumour immunity. Furthermore, they can be armed with various immunomodulatory molecules to further enhance anti-tumour immunity. In this project I aim to exploit these qualities to develop a translatable cancer vaccine. Virus-infected cancer cells were injected subcutaneously in a prime/boost regimen. Dying cancer cells will release the required danger signal leading to dendritic cell activation and cross-presentation of tumour associated antigens to T cells to elicit an anti-tumour immune response. Our results in the murine pancreatic cancer model showed that vaccination with virusinfected DT6606 cells induced tumour specific immunity capable of protecting vaccinated animals against re-challenge with tumour cells. The highest level of interferon gamma production, a surrogate marker of anti-tumour immunity, was achieved when animals were primed with adenovirus-infected cells. There was no significant difference between various boost groups. To enhance the safety of the proposed protocol a secondary treatment was introduced to arrest the proliferation of tumour cells prior to injection. Our results confirmed that secondary treatment with mitomycin does not affect the induction of tumour specific immunity and it does not affect the release of pathogen-associated molecular patterns in the form of viral proteins and DNA. To test our vaccination regimen in head and neck squamous cell carcinoma (HNSCC) we develop a clinically relevant mouse model using SCC7, B4B8 and LY2 cells to replicate various clinical scenarios including locally advancing disease and post excision locoregional recurrence. Vaccinating mice with HNSCC cells pre-infected with our recently developed tumour-targeted triple-deleted adenovirus (AdTD) resulted in a cell-specific antitumour immune response. In addition, it resulted in an increase in effector memory T-cells of both CD4+ and CD8+ phenotypes. Efficacy studies showed our vaccination can significantly slow down the growth rate of tumours in locally advancing disease. This led to increase survival of the vaccinated mice although it did not reach statistical significance. To further enhance the efficacy of our vaccination regimen, we aimed to increase T cell trafficking to the tumour site. CCL25 is a gut homing chemokine. Priming T cells in the presence of CCL25 will lead to upregulation of the surface expression of α4β7 integrin. The latter is a ligand of MAdCAM-1, a cell adhesion molecule highly expressed in the gut and pancreatic tumours. The α4β7/MAdCAM-1 interaction results in preferential homing of activated T cells to these organs. We hypothesised that vaccinating mice with pancreatic tumour cells pre-infected with a CCL25-armed adenovirus will lead to increased T cell trafficking to pancreatic tumours leading to enhanced efficacy. Although we achieved encouraging results in our pilot experiment, we did not detect any significant increase in α4β7 expression once we added a secondary treatment to the vaccination protocol. Similarly, efficacy experiments in the pancreatic cancer transgenic KPC mice did not show any difference in survival between AdTD-CCL25 and the control virus although both groups showed a trend towards increased survival compared to naïve mice. In conclusion, Virus-infected cancer cell vaccine is a potentially promising immunotherapeutic strategy that can be combined with traditional cancer therapies to increase survival of HNSCC and pancreatic cancer patients.

The high incidence of gastrointestinal cancers in the general population and the presence of premalignant dysplastic precursor lesions in the gastrointestinal tract make the gastrointestinal tract an ideal environment to study cancer clonality and clonal expansion. Background: Intestinal metaplastic (IM) glands in the human stomach are clonal, contain multiple stem cells and spread by fission. This mechanism of gland fission causes field cancerisation. We hypothesised that gastric adenocarcinoma (GA) progresses through a series of genetic events arising from a founder mutation. A process analogous to niche succession may also take place in the normal oesophagus. We hypothesise that oesophageal squamous cell cancer occurs by a process of field cancerisation of the oesophagus. RHBDF2 has been identified as the gene responsible for tylosis with oesophageal carcinoma (TOC). We hypothesise that RHBDF2 germline gain of function mutations might be lost during tumour progression in TOC and this might affect iRhom2 localisation in the cell. Methods and results: A cohort of 23 patients with dysplasia and a cohort of 51 GA patients were screened for genes accounting for 75% of all somatic mutations previously reported in GA. Only 13% of dysplastic patients and 31.4% of GA patients had mutations. Three dysplastic patients and six GA patients were analysed by microdissection. Small gastric cancer foci in a cohort of hereditary diffuse gastric cancer (HDGC) patients (n=5) were also screened by laser-capture microdissection (LCM) for mutations in TP53. A cohort of 30 patients was screened for common mutations in OSCC and for RHBDF2 mutations. 36.36% of the patients presented mutations. Three patients with mutations were randomly selected and areas of oesophageal squamous cell dysplasia and OSCC were analysed by LCM. Three TOC patients were also analysed by LCM and immunohistochemistry was performed for iRhom2 and ADAM17. Conclusions: The usual mutational events established for GA development during the metaplasiadysplasia- carcinoma sequence (MCS) do not fit the results from either of our two LCM mutation studies in the human stomach. Dysplasia was shown to be clonal and GA demonstrates genetic heterogeneity through clonal evolution. Field cancerisation could not be detected in HDGC using TP53 as a clonal marker. The low incidence of OSCC patients with mutations implies that other genes may be involved in the premalignant pathway leading to OSCC. Oesophageal squamous cell dysplasia and OSCC demonstrate clonal expansion through tumour progression. RHBDF2 mutations do not occur in sporadic OSCC but germline RHBDF2 mutations can be lost during tumour progression in TOC patients with LOH in 17q. Overall, the somatic mutation theory of carcinogenesis seems to hold true for both the progression to GA and OSCC, as both carcinomas seem to evolve from a single mutated stem cell and acquire genetic heterogeneity as the tumours evolve.

Cancer, a disease of an uncontrolled cell division, growth and metastasis as a result of genetic mutations, environmental factors and host response, is affecting populations worldwide. Etiology, pathogenicity, and genetics related to cancer are not well understood, and treatment has not been as effective as scientists have expected. Continual research is being done to improve current understanding and treatments. Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers (representing >90 % of all head and neck cancers) involving neoplasms of the oral cavity and oropharynx. OSCC is a very pernicious malignancy developed from epithelial cells. There is evidence that a key N-glycosylation gene, DPAGT1, is associated with cancer. Although N-glycosylation of proteins is involved in organ development and homeostasis of tissue, overexpression of DPAGT1 has been implicated in oral cancer initiation and metastasis. Defects in N-glycosylation underlie congenital disorders, while hyper-N-glycosylation has been shown to be a feature of many cancers. The N-glycosylation pathway directs cell adhesion and cytoskeletal dynamics by impacting the function of E-cadherin, a major epithelial cell-cell adhesion receptor. E-cadherin is a tumor suppressor responsible for the organization of multiprotein complexes named adherens junctions (AJs). In epithelial cells, stable AJs are essential for several cellular processes, including inhibition of cell proliferation, reorganization of the actin cytoskeleton, and maintenance of an epithelial phenotype. Indeed, restoration of AJs has been shown to revert cancer cells from a mesenchymal to an epithelial phenotype and to reduce invasiveness. Previous work has shown that upregulation of DPAGT1 plays a pivotal role in driving canonical WNT/β-catenin signaling (also known as canonical Wnt signaling) that represses E-cadherin adhesions and drives tumorigenic phenotypes in oral cancer. This suggests a role in coordinating balance between proliferation and adhesion by DPAGT1. To date, little is known about the molecular and cellular details underlying differences among OSCC cell lines. CAL 27 and HSC-3 are human cancer cell lines commonly used to in laboratory OSCC research. The main differences between these cell lines include capsular tumors formed by CAL27 cells in nude mouse models in contrast to non-capsular and invasive tumors formed by HSC-3 cells. The goal of this study was to characterize biochemical differences between these two cell lines for further research.

HOXA7 belongs to a family of homeobox transcription factors that are master regulators of cell differentiation, morphogenesis during embryonic development and cell proliferation. Dysregulation and non-nuclear localization of these proteins play a role in a large number of solid tumours, with reports of significant upregulation of HOXA7 in oral dysplasia. It is unclear whether HOXA7 induction in solid tumours is causative or if it is a result of oncogenic changes. In this thesis we studied its effect on cell differentiation, growth, stemness, cell migration, EMT and cell senescence. The main hypothesis was that HOXA7 regulated keratinocyte differentiation through the regulation of activator protein 1 (AP-1), a keratinocyte specific activator of differentiation. We also hypothesised that HOXA7 increased the proliferation rate in keratinocytes. In an AP-1 reporter assay in HEK293 cells, HOXA7 was shown to decrease AP-1 activity significantly. The inactivation of AP-1 was not due to inactivation of PKC, as HOXA7 did not interfere with the activation of the kinases in HEK293. More specifically, we reported a very significant repression of c-Jun and JunD promoter activity in the presence of ectopic HOXA7 in HEK293 cells. We further showed that this mechanism might also be applicable in keratinocytes, as HOXA7 inhibited the transcription of AP-1 subunits of both the Jun and Fos family in skin keratinocytes. Furthermore, we showed transcriptional repression of four differentiation markers and a downregulation of K1 and FLG protein in transduced NEB-1 monolayers as well as K1 suppression in HaCaT cells. The organotypic cultures revealed a downregulation of K1, K10, and filaggrin in stratified HaCaT cells by HOXA7. There was however no downregulation in oral keratinocytes. These observations taken together suggested that HOXA7 repressed the synthesis of AP-1 units in skin keratinocytes, which would have resulted in reduced quantities of AP-1 and therefore lower activity. Contrary to previous reports, we observed no positive involvement of HOXA7 in keratinocyte proliferation, EMT or migration. There was however an indication of cell-type specific MET and induced cell senescence. Based on our results we propose a cell-type specific role of HOXA7 as an antagonist of AP-1 transcription in skin keratinocytes, and a possible direct binding of HOXA7 to c-Jun and JunD promoters.

O carcinoma espinocelular de cabeça e pescoço (CECP) é um problema de saúde pública que apresenta alta taxa de mortalidade, frequentemente relacionado à presença de recorrências locais e metástases. A descoberta de um pequeno subconjunto de células tumorais com características semelhantes às células-tronco, conhecidas como células-tronco tumorais (CTTs), tem sido relatadas como as principais responsáveis pelo início, progressão e recidiva do CECP. O processo de metástase nestas neoplasias é bastante complexo e envolve o desprendimento de células epiteliais tumorais do local de aparecimento primário devido à subexpressão ou superexpressão de algumas proteínas específicas nestas células, caracterizando um processo conhecido como transição epitélio-mesenquimal (EMT). A compreensão dos mecanismos envolvidos no processo de EMT têm sido investigados para o desenvolvimento de terapias específicas. O ácido retinoico (AR) vem sendo empregado em diversas terapias devido a sua capacidade de controlar a proliferação e promover diferenciação celular, entretanto, anormalidades na expressão ou função de seus receptores são relatadas em muitos tipos de células do câncer. Este estudo tem por objetivo correlacionar a expressão de marcadores do processo de EMT, marcador de célula tronco tumoral (ALDH1) e receptores do ácido retinoico e de retinoide X (isoformas α e β) em amostras teciduais provenientes de portadores de CECP primários, além, de correlacionar os resultados obtidos com os parâmetros clínicos, características histopatológicas e prognóstico destes pacientes em um período de acompanhamento de 7 anos. / The head and neck squamous cell carcinoma (HNSCC) is a public health problem that presents high mortality rates in relation to the presence of local recurrences and metastases. A finding of a small subset of tumor cells with stem like-cells characteristics, known as cancer stem cells (CTTs), has been reported as being primarily responsible for the onset, progression and recurrence of CECP. The metastasis process in these neoplasms is quite complex and involves the tumor epithelial cells detachment from the primary site of appearance due to underexpression or overexpression of some specific proteins in these cells, characterizing the epithelial-mesenchymal transition (EMT) process. An understanding of the mechanisms involved in the EMT process has been investigated for the development of specific therapies. Retinoic acid (AR) has been used in several therapies because its ability to control the proliferation and promote cell differentiation, however, abnormalities in the expression and function of its receptors are reported in many types of cancer cells. The aim of this study was to correlate the expression EMT process markers, tumor stem cell marker (ALDH1), retinoic acid and retinoic acid X receptors (α and β isoforms) in tissue samples from primary CECP, in addition, to correlate the results with the clinical parameters, histopathological and prognostic characteristics of these patients in a 7 years follow-up.