Upregulation of tropomyosin alpha-4 chain in patients' saliva with oral squamous cell carcinoma as demonstrated by Phage display.

Patients with oral squamous cell carcinoma (OSCC) present significant alterations in their saliva proteome. We have used the shotgun Phage Display (PD) technology to identify candidate proteins that were upregulated in saliva of OSCC by selecting ligands to salivary proteins from a single-chain variable fragment (scFv) PD combinatorial library. After two selection cycles, the highly reactive clone scFv-D09 was able to distinguish saliva of OSCC patients from healthy subjects by enzyme-linked immunosorbent assay (ELISA) with sensitivity and specificity of 96.67%. Additionally, the scFv-D09 clone presented a positive immunostaining for invasive malignant epithelial cells in the connective tissue, keratin pearls in the OSCC, and ducts of salivary glands. We have further identified the target protein as the tropomyosin alpha-4 chain (TPM4) by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry, and its binding to the scFV-D09 was demonstrated by bioinformatics. Briefly, we have identified TPM4 as upregulated salivary protein in patients with OSCC, which plays a central role in stabilizing cytoskeleton actin filaments, probably linked with tumor tissue remodeling. Long-term longitudinal studies are needed to validate TPM4 as a potential marker of a malignant process.

Pathologic significance of AKT, mTOR, and GSK3ß proteins in oral squamous cell carcinoma-affected patients.

Phosphatidylinositol-3-kinases are kinases that lead to AKT phosphorylation and thus mTOR and GSK3ß activation. These proteins are linked to tumorigenesis, but their roles in driving cervical lymph node (CLN) metastasis of oral squamous cell carcinoma (OSCC) cells are unknown. This study aimed to investigate the role of AKT, mTOR, and GSK3ß proteins in the occurrence of CLN metastasis in OSCC patients. Ninety and 18 paraffin-embedded OSCC and oral mucosa samples were included, respectively. We divided our OSCC patients into non-metastasizing (PNM) and metastasizing (PM) groups, and the expression of total AKT, pAKT1Thr308, pAKTSer473, GSK3ß, pGSK3ßSer9, and pmTORSer2448 was analyzed by immunohistochemistry. The mean expression of GSK3ß, pGSK3ßSer9, total AKT, and pmTOR2448 was always higher in the OSCC tissues than that in the controls. A positive correlation was also found among these proteins. Total AKT, pmTORSer2448, and pGSK3ßSer9 expression was significantly higher in the PNM and PM groups than that in the control group. However, only GSK3ß expression was significantly higher in the PM group compared with the PNM group. High expression levels of GSK3ß and pGSK3ßSer9 were significantly associated with CLN metastasis, but only GSK3ß remained an independent predictor of CLN metastasis. pGSK3ßSer9 and CLN metastasis were associated with a poor prognosis, but only the latter remained an independent prognostic parameter. Kaplan-Meier survival curves showed that pGSK3ßSer9 and CLN metastasis were significantly related to reduced survival rates. These results suggest that AKT and mTOR proteins are involved in OSCC biology and that GSK3ß itself may drive CLN metastatic spread of OSCC cells.

Primary amelanotic mucosal melanoma of the oronasal region: report of two new cases and literature review.

Primary amelanotic mucosal melanoma is a rare entity with challenging histopathological features. Because these tumors are thought to be biologically more aggressive, they have a poorer prognosis than that of pigmented melanomas. In this work, we present a literature review about the clinical, histopathological, and immunohistochemical features of primary amelanotic mucosal melanoma of the oronasal region and report two new cases. Amelanotic mucosal melanoma commonly affects men in the seventh decade of life and tend to have a poor prognosis, as seen by the high incidence of metastasis, recurrences, and, ultimately, death. There is a similar pattern in the clinic-pathological predilections (such as age, gender, primary site, and metastatic potential) of amelanotic mucosal melanoma when comparing with data reported for pigmented lesions. This work reinforces knowledge about amelanotic mucosal melanomas and epidemiologic predilections. The optimal management of this lesion remains controversial.

An antibody-like peptide that recognizes malignancy among thyroid nodules.

There is an urgent need for biomarkers to identify malignant thyroid nodules from indeterminate follicular lesions. We have used a subtractive proteomic strategy to identify novel biomarkers by selecting ligands to goiter tissue from a 12-mer random peptide phage-displayed library using the BRASIL method (Biopanning and Rapid Analysis of Selective Interactive Ligands). After three rounds of selection, two highly reactive clones to the papillary thyroid tumor cell line NPA were further evaluated, and their specific binding to tumor proteins was confirmed using phage-ELISA. The antibody-like peptide CaT12 was tumor-specific, which was further tested by immunohistochemistry against TMAs (tissue microarrays) comprised of 775 human benign and malignant tissues, including 232 thyroid nodular lesions: 15 normal thyroid tissues, 53 nodular goiters (NG), 54 follicular adenomas (FA); 69 papillary thyroid carcinomas (PTC); and 41 follicular carcinomas (FC). CaT12 was able to identify PTC among thyroid nodular lesions with 91.2% sensitivity and 85.1% specificity, despite its non-specificity for thyroid tissues. Additionally, the CaT12 peptide helped characterize follicular lesions distinguishing the follicular variant of PTC (FVPTC) from FA with 91.9% accuracy; FVPTC from NG with 83.1% accuracy; FVPTC from the classic PTC with 57.7% accuracy; and FVPTC from FC with 88.7% accuracy. In conclusion, our strategy to select differentially expressed ligands to thyroid tissue was highly effective and resulted in a useful antibody-like biomarker that recognizes malignancy among thyroid nodules and may help distinguish follicular patterned lesions.

Expression of annexin A1 mRNA in peripheral blood from oral squamous cell carcinoma patients.

Several studies have been suggesting annexin A1 protein as an active player in tumorigenesis of many organs. Nevertheless, its tumor biomarker role has been mainly studied in tissues by immunohistochemistry or cell culture. Hence, in this investigation, the peripheral blood from 27 oral squamous cell carcinoma (OSCC) patients and 25 negative control individuals were examined by quantitative real-time PCR. Down-regulated ANXA1 expression at mRNA level was observed in OSCC samples (p=0.026). Significantly diminished mRNA levels correlated to age, sex and the anatomical site of the tumor lesion were observed. Moreover, the ROC curve analysis revealed the performance of ANXA1 expression as a suitable biomarker for patients with oral cavity cancer, especially those with 60years of age or older and/or women. For the first time, ANXA1 mRNA is revealed as blood-based biomarker, and its adoption for complementary non-invasive diagnosis of OSCC is suggested. These results suggest that, beyond the anti-inflammatory function, annexin A1 may also play a tumor suppressor role in peripheral blood cells, such as leukocytes.

Myoepithelial carcinoma of the submandibular gland: report of a case with multiple cutaneous metastases.

Myoepithelial carcinoma is a rare and aggressive neoplasm of the salivary glands. One-third of the patients may develop regional distant metastases, and lungs and kidneys have been regarded as the most usual sites for implantation. There is, however, little information on the metastatic behavior of this malignancy. We report the first case of patient with multiple cutaneous metastases from a myoepithelial carcinoma of the submandibular gland, which depicted a very aggressive clinical course.

Avaliação do perfil do diagnóstico de câncer bucal após a implantação do Programa de Cuidados Específicos às Doenças Estomatológicas / Evaluation of diagnostic profile in oral cancer after the implantation of aCare Program for Specific Diseases in Stomatology

Introdução: Câncer de boca é um termo utilizado para designar o grupo de neoplasias malignas incidentes nos tecidos bucais. É um importante problema de saúde pública em várias partes do mundo, situando-se entre os dez mais comuns tipos de cânceres humanos. Estudos epidemiológicos revelam que ainda persiste um perfil de diagnóstico tardio para a doença, fato que desfavorece marcadamente o prognóstico. Nesse sentido, é fundamental que todos os esforços sejam concentrados na mudança desse perfil de diagnóstico, a fim de favorecer diagnósticos mais precoces. Objetivo: Avaliar o perfil de diagnóstico do câncer bucal na Faculdade de Odontologia da Universidade Federal de Uberlândia, após a implantação do Programa de Cuidados Específicos a Doenças Estomatológicas. Método: Casos de carcinomas epidermóides bucal diagnosticados em períodos anteriores (1993-1997) e posteriores (1999-2004 e 2008-2010) à instalação do referido programa foram analisados quanto aos dados sociodemográficos dos pacientes e clinicopatológicos das lesões, considerando, principalmente, o estadiamento da doença. Resultado: O perfil dos diagnósticos do câncer manteve-se inalterado, independentemente do período estudado. Houve um predomínio de lesões entre 2 e 4 cm, sendo que, no último período (2008-2010), prevaleceu o diagnóstico de lesões maiores do que 4 cm (p = 0,0132). Além disto, o diagnóstico predominante incluiu lesões em estágios avançados, ressalvando-se que, no período imediato à instalação do programa, houve um predomínio significativo de lesões em estágio precoce (p < 0,0001). Conclusão: Esses resultados mostraram que não houve uma significativa modificação do perfil do diagnóstico após a implantação do Programa de Cuidados Específicos a Doenças Estomatológicas.

Background: Oral cancer is a term used to designate the group of malignancies incidents in oral tissue. It is a major public health problem in many parts of the world, standing among the ten most common types of human cancers. Epidemiological studies show that there is still a pattern of late diagnosis for the disease. In this sense, it is essential that all efforts are concentrated on changing this pattern of diagnosis, in order to facilitate early diagnosis. Objective: To evaluate the diagnostic profile of oral cancer in the Faculty of Dentistry, Federal University of Uberlandia, after the implantation of Care Program Specific Diseases in Stomatology. Method: For both cases of oral squamous cell carcinoma diagnosed in the periods before (1993-1997) and after (1999-2004 and 2008-2010) the installation of this program were analyzed for patients? sociodemographic data and clinical-pathological lesions, considering especially the staging of the disease. Result: Our results showed that, overall, the profile of cancer diagnoses remained unchanged, regardless of the period studied. There was a predominance of lesions between 2 and 4 cm, and in the last period (2008-2010), the prevailing diagnosis of lesions larger than 4 cm (p = 0.0132). Furthermore, the predominant diagnosis included lesions in advanced stages, stressing that, in the immediate installation of the program, there was a significant predominance of lesions at an early stage (p < 0.0001). Conclusion: These results showed no significant change in the profile of the diagnosis after the implementation of care program for specific diseases in stomatology.

Metachronous bilateral pleomorphic adenoma of the parotid gland.

Bilateral salivary gland tumors are very rare, accounting for 3% of all parotid gland tumors. Although the most common tumor with bilateral development is the Warthin tumor, pleomorphic adenomas (PA) have been diagnosed simultaneously as well, but in a smaller incidence. Because of this, the prevalence, etiology, pathogenesis, and behavior of the PA in this context are poorly understood. We present a case of bilateral metachronous PA affecting the parotid gland in a 63-year-old woman. Clinically, the lesions presented with similar aspects as seen in cases of solitary PA with slow-growing asymptomatic nodule. Both lesions were diagnosed by fine-needle aspiration biopsy at an interval of 2 years between them. A total and superficial parotidectomy for left and right tumors, respectively, was performed. Only on the left side some facial nerve branches were removed that induced partial paralysis in the patient. A review of the pertinent literature is included.

Clinical presentation of patients with oral squamous cell carcinoma when first seen by dentists or physicians in a teaching hospital in Brazil.

The ability to diagnose oral cancer depends in part on the knowledge, attitudes, and practices of the health professional. On the other hand, the patients' choice of health professional depends on their perceptions of the ability of such professionals to diagnose and treat what they believe their health problem is. In this study, we investigated the clinical profiles of patients with oral cancer ( n=354) when first seen by dentists ( n=129) or physicians ( n=225) in a teaching hospital. The charts of patients with oral squamous cell carcinoma were analyzed for the following variables: age, sex, race, signs and symptoms by the time of presentation to the health professional, size and site of the tumor since first manifestation, and clinical stage of the disease. Our results demonstrate that dentists and physicians assessed patients comparably regarding age, sex, and race. Patients complaining of dysphagia and odynophagia were seen more often by physicians than dentists (45/225 vs 9/129 [20.0% vs 7.0%] and 30/225 vs 4/129 [13.3% vs 3.1%], respectively), whereas those with local pain and burning preferentially sought dentists (77/129 vs 56/225 [59.7% vs 24.9%] and 4/129 [3.1%] vs 0/225, respectively). Physicians diagnosed oropharyngeal (45/208 vs 9/116 [21.6% vs 7.8%]) and lip lesions (71/208 vs 7/116 [34.1% vs 6.0%]) more often, whereas dentists saw more cases of cancer of the alveolar ridge (42/116 vs 7/208 [36.2% vs 3.4%]) and floor of the mouth (19/116 vs 10/208 [16.4% vs 4.8%]). Our findings suggest that patients have different perceptions of the roles of dentists and physicians regarding the ability to diagnose and treat oral lesions. Signs, symptoms, and location of the cancer lesions appear to be the most important variables associated with the choice of health professional.

Trauma faringo-laríngeo aberto / External laryngopharyngeal trauma

Este trabalho se refere a um caso de trauma perfurante no pescoço devido à chifrada de boi, em que houve fratura da cartilagem tireóide, desinserção das pregas vocais, laceração da parede posterior da hipofaringe e fratura de corpo vertebral (C4) sem lesão do canal medular.No trauma aberto de laringe, o paciente pode apresentar alterações da voz, disfagia, dispnéia, estridor, enfizema subcutâneo, hemoptise ou fratura da cartilagem tireóide, podendo evoluir com estenose, disfonia, aspiração e morte. O relato do caso é importante por ser um trauma perfurante com etiologia pouco freqüente e, apesar da gravidade, o paciente evoluiu sem seqüelas.

This report describes a case of a perforation trauma of neck caused by a bull's horns attack, with fracture of the thyroid cartilage, disinsertion of the vocal folds, laceration of the hypopharynx and fracture of the vertebral body (C4) without lesion of the medullar channel. A patient with laryngeal open trauma can show voice alterations, dysphagia, dyspnea, stridor, subcutaneous emphysema, hemoptysis, fracture of the thyroid cartilage and later with stenosis, dysphonia, aspiration and death. The relevance of this report is due to its low frequent etiology and, in spite of its graveness the patient recovered without sequels.

Osteíte fibrosa cística causando paraplegia crural / Crural paraplegia for osteitis fibrosa cystica

A osteíte fibrosa cística é uma apresentação avançada do hiperparatireoidismo e pode acometer, mais raramente, a coluna vertebral. No presente relato, a paciente evoluiu de um quadro de dor localizada para paraplegia por compressão medular. Destaca-se a importância de investigação e abordagem precoces dessa condição, a fim de evitar complicações irreversíveis.

Osteitis fibrosa cystica is an advanced consequence of hiperparathyroidism and, eventually, it is situated in spine. In this report, the patient showed a localized pain which quickly evaluated to paraplegia caused by spinal cord compression. Early investigation and intervention in this clinical condition are important in order to prevent irreversible complications.

Metástase óssea em coluna torácica de carcinoma papilífero de tireóide como apresentação inicial de doença / Bone metastases in thoracic spine from papillary thyroid carcinoma at initial presentation

Os carcinomas diferenciados da tireóide geralmente não são agressivos, sendo o carcinoma papilífero o mais freqüente dentre eles. O carcinoma papilífero causa metástases ósseas com freqüência variando entre 1,4% e 7%. Relatamos o caso de uma paciente portadora de carcinoma papilífero de tireóide, cujo achado inicial era uma metástase na coluna torácica.

Differentiated thyroid carcinomas generally are not aggressive, being the papillary carcinoma the most frequent among them. The papillary carcinoma causes bone metastases with a frequency varying from 1.4% to 7%. We repot a case of a patient with a papillary thyroid carcinoma, whose initial presentation was a thoracic spine metastases.