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.

No description available.

In this study, we investigated the mechanisms by which PBRM1 functions as a tumor suppressor in clear cell renal cell carcinoma. PBRM1, also known as BAF180 or Polybromo, is a member of the PBAF SWI/SNF chromatin remodeling complex. Cancer sequencing studies have revealed that SWI/SNF components are widely mutated in cancer. PBRM1 is recurrently mutated in various human malignancies, but it has a particularly high mutation rate in clear cell renal cell carcinoma: ~40% of clear cell renal cell carcinomas have a PBRM1 mutation, making it the second most highly mutated gene in clear cell renal cell carcinoma behind VHL. Although many recent studies have looked at how other SWI/SNF components function in cancer control, relatively little is known about the tumor suppressive mechanisms of PBRM1 in clear cell renal cell carcinoma. To investigate PBRM1 function, we manipulated its expression in clear cell renal cell carcinoma cell lines. In cell lines with intact PBRM1, we stably knocked down its expression using shRNA. In a cell line with mutant PBRM1, we stably restored expression of the wild-type protein. We found that PBRM1 deficiency significantly enhanced the growth properties of cells, but only when the cells were grown under stressful conditions, such as reduced serum or a 3-D culture environment. To investigate genes and pathways influenced by PBRM1 that may confer this growth advantage, we compared gene expression differences in the clear cell renal cell carcinoma cell lines and murine embryonic fibroblasts with or without PBRM1. We found that PBRM1 regulated numerous cancer-related genes and pathways. One gene, ALDH1A1, was consistently upregulated with PBRM1 deficiency across our cell lines. Further expression analysis using two different clear cell renal cell carcinoma primary tumor datasets revealed that PBRM1 mutation in primary tumors was also associated with higher ALDH1A1 levels. ALDH1A1, or aldehyde dehydrogenase 1, is part of the retinoic acid metabolic pathway and irreversibly converts retinaldehyde to retinoic acid. It functions in hematopoietic stem cell development, white versus brown fat programming, and insulin signaling. Numerous studies have also identified ALDH1A1 as a marker of tumor-initiating cells, also known as cancer stem cells. Not much is known about the regulation of ALDH1A1 expression in cancer, and it has not previously been linked to PBRM1 or SWI/SNF. We confirmed that stable knockdown of PBRM1 in clear cell renal cell carcinoma cell lines resulted in higher ALDH1A1 mRNA and protein expression, and also higher ALDH1-class enzyme activity. Alternatively, re-expression of wild-type PBRM1, but not cancer-associated mutant PBRM1, lowered ALDH1A1 expression and activity in the PBRM1-mutant line. Additionally, inhibiting ALDH1A1 or knocking it down in the context of PBRM1 deficiency reduced anchorage-independent growth, while over-expressing ALDH1A1 in the PBRM1-normal setting increased tumorsphere-forming capacity. These results suggest that ALDH1A1 is not only a marker of tumor-initiating cells, but can also increase the tumorigenic potential of cells. Based on our gene expression analysis, we additionally explored PBRM1 regulation of the EGFR and IFN pathways. PBRM1 decreased total EGFR protein levels and dampened downstream signaling. These changes had functional consequences, as PBRM1 deficiency led to faster growth in response to EGF stimulation. However, it did not create a setting of oncogenic addiction, as PBRM1 deficient cells were also more resistant to EGFR inhibition. Alternatively, PBRM1 deficiency reduced basal and IFNα-induced levels of IFI27, a pro-apoptotic interferon response gene, and made cells more resistant to growth inhibition by IFNα. PBRM1 mutations in cancer would thus be expected to have wide-ranging effects on a cell, and the targeting of any one specific downstream pathway might have limited efficacy. Finally, we investigated the molecular mechanisms of how PBRM1 deficiency could alter transcription, keeping in mind that PBRM1 is one subunit of the larger PBAF complex. In our clear cell renal cell carcinoma cell lines, we found that mRNA and protein levels of another PBAF-specific subunit, ARID2, increased with PBRM1 deficiency. PBRM1 mutation in primary tumors was also associated with significantly higher ARID2 expression. Immunoprecipitation and glycerol gradient fractionation experiments suggested that more ARID2 may associate with the SWI/SNF components BRG1 and SNF5 after PBRM1 knockdown. ARID2 ChIP-seq analysis revealed that this remnant PBAF-like complex was bound to fewer locations in the genome, and its binding locations were broadly redistributed. Both gained and lost ARID2 binding were associated with differential gene expression, of both upregulated and downregulated genes, indicating that the genomic context influences whether PBAF-binding is activating or repressive. Interestingly, we also found that ARID2 was required for some of the pro-tumorigenic changes associated with PBRM1 deficiency, such as upregulation of ALDH1A1 and EGFR levels, but not others, such as decreased IFI27 levels, implying alternative modes of transcriptional regulation. In total, this study implicates PBRM1 in the regulation of numerous cancer-related genes and pathways in clear cell renal cell carcinoma. PBRM1 mutation would alter the genomic binding of a residual PBAF-like complex containing ARID2, leading to transcriptional changes that promote tumor formation and growth. A better understanding of this oncogenic mechanism may reveal novel therapeutic opportunities.

A instabilidade genética é um importante evento associado ao carcinoma epidermóide de boca, sendo alterações na região cromossômica 11q constantemente relatadas. Neste estudo, genes localizados na região cromossômica 11q, especificamente os genes CTTN, PPFIA1, SHANK2, TAOS1 e MMP-7, foram investigados quanto a diferenças de expressão de transcritos entre carcinomas epidermóides de boca e suas margens correspondentes. A expressão desses genes foi relacionada com aspectos clínicos e histológicos, com critérios de agressividade estabelecidos, e com a sobrevida dos pacientes. Foram analisadas pela técnica de qRT-PCR 29 amostras congeladas de tumores e 25 margens. Todos os genes apresentaram maiores valores de expressão nos tumores em comparação com as margens, embora apenas o gene MMP-7 tenha exibido valores estatisticamente significantes. A expressão do gene MMP-7 mostrou fraca associação com tumores menos agressivos, e os outros genes apresentaram maiores valores de expressão em tumores mais agressivos, sem significância estatística. Não houve diferença estatística entre a freqüência das variáveis clínicas e histopatológicas com a expressão dos genes estudados, porém o PPFIA1 demonstrou maiores níveis de expressão em tumores de assoalho. Em relação à sobrevida, a expressão elevada de PPFIA1 pode implicar em um maior risco de óbito. Assim, é possível a participação do gene MMP-7 no desenvolvimento da neoplasia, e a relação do PPFIA1 com o risco de óbito, porém a expressão de transcritos dos genes CTTN, SHANK2, TAOS1 e MMP-7 não pode ser relacionada com agressividade tumoral e prognóstico. / Genetic instability is an important event associated with oral squamous cell carcinoma, and alterations in the chromosome region 11q are constantly reported. In this study, genes located on chromosome region 11q, specifically genes CTTN, PPFIA1, SHANK2, TAOS1 and MMP-7, were investigated for differences in the expression of transcripts in oral squamous cell carcinoma and their corresponding margins. The expression of these genes was correlated with clinical and histological aspects, aggressiveness criteria established, and with patient survival. Twenty-nine frozen samples of tumors and 25 samples of margin tissue were analyzed using qRT-PCR. All genes showed a higher expression in tumors, compared with the margins, although only the MMP-7 gene demonstrated statistically significant values. The expression of the MMP-7 gene showed weak association with less aggressive tumors, and the other genes showed higher expression in more aggressive tumors, without statistical significance. There was no statistical difference between the frequency of clinical and histopathological variables and the expression of genes studied, however the PPFIA1 gene demonstrated higher levels of expression in tumors of the floor of mouth. With regard to survival, the high expression of PPFIA1 may imply a greater risk of death. Thus, it is possible that the MMP-7 gene participates in the development of malignancy, and PPFIA1 expression may also be associated with risk of death, however, the expression of transcripts of the CTTN, SHANK2, TAOS1 and MMP-7 genes may not be related to tumor aggressiveness and prognosis.

O carcinoma de células escamosas de cavidade bucal tem alta prevalência e índice de mortalidade considerável entre as principais neoplasias malignas. Acredita-se que carcinógenos químicos promovem a carcinogênese através de danos oxidativos e mutações genéticas, entre outros mecanismos. O organismo evita o acúmulo de espécies reativas de oxigênio (EROs), ou seja, o estresse oxidativo, através da produção endógena de antioxidantes como o -tocoferol, o retinol e a glutationa. Diversos estudos têm demonstrado que a administração de glutamina pode aumentar a produção de glutationa, proteger células de danos oxidativos e alterações genéticas, e, assim, inibir ou retardar a carcinogênese. Esse aminoácido é considerado um agente quimiopreventivo por atuar em alvos moleculares e celulares específicos, no processo de inflamação ou transdução de sinais, além de induzir atividade de enzimas de detoxificação e suprimir proliferação celular. O protocolo de indução de carcinogênese bucal induzida por DMBA, dimetilbenzantraceno dilúido em acetona, aplicado três vezes por semana, foi bem estabelecido em hamsters e sabe-se que a formação de EROs durante sua metabolização pode se difundir a partir do local de geração, para fora da célula, e iniciar a cadeia de peroxidação lipídica. Sabe-se que existe metabolização hepática do DMBA quando aplicado em mucosa jugal. Nesse estudo avaliou-se o efeito da suplementação de glutamina via oral e intragástrica em carcinogênese DMBA-induzida em mucosa de bolsa jugal de hamsters. Dosaram-se níveis de malondialdeído (MDA), principal produto de peroxidação lipídica, e antioxidantes -tocoferol, retinol e glutationa. Obteve-se como resultado a formação de carcinoma de células escamosas na maioria dos animais, independentemente da administração de glutamina, na dosagem testada. Não foram observadas diferenças na quantidade de MDA, glutationa, proteína e retinol no fígado dos animais. Tampouco houve diferença entre os níveis plasmáticos de glutationa entre os grupos. Esses resultados demonstram que não houve estresse oxidativo significativo nos tecidos testados. Porém houve acúmulo de -tocoferol no fígado dos animais tratados com o carcinógeno por 15 semanas, independentemente da administração de glutamina. Conclui-se, portanto, que pode ter ocorrido agressão ao tecido hepático desses animais e que a glutamina não foi eficiente na prevenção de carcinogênese ou agressão hepática. Possivelmente o tecido tumoral apresentaria alteração do equilíbrio oxidante/antioxidante, mas não foi avaliado nesse estudo. / Oral cavity squamous cell carcinoma has a high prevalence and substantial mortality rate among the major malignancies. It is believed that chemical carcinogens promote carcinogenesis by oxidative damage and mutation, among other mechanisms. The body prevents the accumulation of reactive oxygen species (ROS), oxidative stress, through the production of endogenous antioxidants such as -tocopherol, retinol, and glutathione. Several studies have demonstrated that glutamine administration can increase the production of glutathione, protecting cells from oxidative damage and genetic changes, and thus inhibit or delay the carcinogenesis. This amino acid is considered a chemopreventive agent to act on specific molecular and cellular targets, in inflammation or signal transduction, and activity to induce detoxification enzymes and suppress cell proliferation. The dimethylbenzanthracene (DMBA) induced carcinogenesis protocol consists in three times a week application of DMBA diluted in acetone, in hamsters. It is known that the formation of ROS during its metabolism can diffuse from the site of generation, outside the cell, and initiate the lipid peroxidation chain. It is known that there is hepatic metabolism of DMBA when applied to the buccal mucosa. This study evaluated the effect of oral and intragastric glutamine supplementation in DMBA-induced carcinogenesis on the cheek pouch mucosa of hamsters. Levels were assayed for malondialdehyde (MDA), the main product of lipid peroxidation, and the antioxidants -tocopherol, retinol and glutathione. The results show the formation of squamous cell carcinoma in most animals, regardless of this glutamine amount administration. There were no differences in the amount of MDA, glutathione, protein and retinol in the liver of animals. There was no difference between plasma levels of glutathione between groups. These results demonstrate that there was no significant oxidative stress in the tissues tested. However, there was accumulation of -tocopherol in the liver of animals treated with the carcinogen for 15 weeks, regardless of the administration of glutamine. Therefore that may have occurred aggression liver tissue of animals and that glutamine was not effective in the prevention of carcinogenesis or liver injury. Possibly the tumor tissue present shift in the balance oxidant / antioxidant, but it was not evaluated in this study.

O carcinoma basocelular (CBC) é uma neoplasia cutânea maligna de baixo potencial metastatizante, originada das células da camada basal da epiderme. Sua importância clínico-epidemiológica pode ser constatada pelo fato de constituir a neoplasia maligna mais comum na espécie humana, cujo principal fator etiológico é a exposição à radiação ultravioleta. Apesar da baixa incidência de metástases, a neoplasia pode adotar um comportamento localmente agressivo, com comprometimento de estruturas profundas e de forte apelo estético, como ocorre na região periocular. Uma das complicações advindas de sua infiltração neste sítio anatômico consiste na invasão de tecidos orbitários cujo tratamento é a exenteração, conduta mutiladora que consiste na retirada do globo ocular e das partes moles da órbita acometida. O objetivo deste estudo foi avaliar os casos de CBC com invasão orbitária que foram submetidos à exenteração no Hospital de Clínicas de Ribeirão Preto, no período de 1992 a 2012, para a possível identificação de fatores clínicos e morfológicos que possam predizer uma evolução desfavorável da neoplasia. Foi realizada uma coleta de dados clínicos, epidemiológicos e histopatológicos dos casos submetidos à exenteração a partir dos prontuários médicos dos pacientes. As lâminas referentes aos exames anátomo-patológicos foram revistas e foi realizado estudo imuno-histoquimico para os marcadores p53, bcl-2, actina de músculo liso e metaloproteinase-1. O grupo controle foi composto por pacientes com diagnóstico da neoplasia em topografia periocular, sem sinais de invasão orbitária. Para os casos com invasão orbitária o número de casos positivos marcados para p53 (0,21) e para actina de músculo liso (0,21) foi significantemente menor que o número de casos positivos para bcl-2 (0,63) e MMP-1 (0,58) (p= 0,0331). Entretanto, o número de casos positivos para bcl-2 (0,63) foi significantemente maior que o número de casos marcados por MMP-1 (0,58) (p=0,0126). Para os tumores sem invasão orbitária, o número de casos positivos para p53 (0,31) e actina (0,31) foi significantemente menor que o número de casos positivos para bcl-2 (0,63) eMMP-1 (0,50) (p=0,0273). Os resultados indicam que a invasão orbitaria por carcinoma basocelular palpebral ocorre com maior frequência no sexo masculino, em pacientes com longa história clínica de múltiplas lesões e submetidos a múltiplos procedimentos. Além disso, os marcadores estudados aparentemente não podem predizer um comportamento mais agressivo do tumor. / Basal cell carcinoma (BCC) is a malignant skin cancer of low metastasizing potential originated from the basal cells of the epidermis. Its clinical and epidemiological importance is evidenced by the fact that it is the most common malignancy in humans and it has as the main etiological factor the exposure to ultraviolet radiation. Despite the low incidence of metastases, the cancer can adopt a locally aggressive behavior with involvement of deep structures and it can have a strong aesthetic appeal, as in the periocular region. One of the complications arising from its infiltration in this anatomical site consists of orbital tissue invasion whose treatment is exenteration, a mutilating procedure consisting of the removal of the eyeball and the soft tissue of the affected orbit. The aim of this study was to evaluate the cases of BCC with orbital invasion that underwent exenteration at the Clinics Hospital of Ribeirão Preto Medical School, University of Sao Paulo, from 1992 through 2012, for possible identification of clinical and morphological factors that can predict an unfavorable evolution of the tumor. The clinical data were obtained from the patients\' charts and we have reviewed all the slides from exenteration specimens and performed immunohistochemical studies with p53, bcl-2, smooth muscle actin and metalloproteinase-1(MMP-1). The control group consisted of age-matched patients with eyelid basal cell carcinomas without orbital invasion. For cases with orbital invasion the number of positive cases labeled for p53 (0.21) and actin (0.21) was significantly lower than the number of positive cases for bcl-2 (0.63) and MMP -1 (0.58) (p = 0.0331). However, the number of positive cases for bcl-2 (0.63) was significantly greater than the proportion of positive cases for MMP-1 (0.58) (p = 0.0126). For cases without orbital invasion the number of positive cases for p53 (0.31) and actin (0.31) was significantly lower than the number of positive cases for bcl-2 (0.63) and MMP-1 (0.50) (p = 0.0273), even though the number of positive cases marked for MMP-1 (0.50) was not significantly different from number of positive cases for bcl-2 (0.63) (p = 0.059). The results indicate that orbital invasion of basal cell carcinoma of the eyelid was more frequent in male sex and that the patients have usually a long history of multiple lesions and were submitted to several procedures. In addition, our results suggest these markers can not predict an aggressive behavior for basal cell carcinomas of the periocular region.

O carcinoma epidermóide da mucosa oral (CEMO) é uma neoplasia maligna comum; no Brasil, são estimados, para 2016, 15.490 novos casos. A invasão óssea ocorre em casos avançados.; esta é classificada em erosiva e infiltrativa. Aparentemente, o processo de transição epitélio-mesenquimal, com o envolvimento da E-caderina, é implicado. Foi investigada a expressão de E-caderina, por meio da imunoistoquímica em 15 casos avançados de CEMO e avaliada sua correlação com as características clínicas e histológicas da invasão óssea. A imunoexpressão da E-caderina foi estudada nos 15 casos de CEMO com evidência histológica de invasão óssea. A maioria dos pacientes eram homens (10 pacientes) e apresentavam invasão em mandíbula (9 casos). A expressão de E-caderina foi negativa em CEMOs com invasão erosiva e positiva nos casos que apresentavam infiltração óssea. A expressão de E-caderina na invasão óssea sugere que a participação do fenômeno de transição epitélio-mesenquimal é um fator diretamente envolvido com o tipo de invasão óssea. / Oral squamous cell carcinoma (OSCC) is a common malignancy; in Brazil it is estimated, in 2016,15.490 new cases. Bone invasion occurs in advanced cases; it is classified in erosive and infiltrative patterns. Apparently, the epithelial-mesenchymal phenomenon, with important participation of E-cadherin is implicated. We investigated the expression of E-cadherin in advanced OSSC and correlated its expression with the clinical characteristics and histologic patterns of bone invasion. Immunoexpression of E-cadherin was studied in 15 cases of OSCC with histological evidence of bone invasion. Most patients were men (10 patients) and presented mandible invasion (9 cases). The expression of E-cadherin was negative in OSCC in erosive bone invasion and positive in the infiltrative bone invasion. E-cadherin expression in bone invasion suggests that participation of epithelial-mesenchymal phenomenon is dependent on the patterns of tumour bone invasion.