Paulo Rogério de Faria

Far beyond the usual biomarkers in breast cancer: a review.

Research investigating biomarkers for early detection, prognosis and the prediction of treatment responses in breast cancer is rapidly expanding. However, no validated biomarker currently exists for use in routine clinical practice, and breast cancer detection and management remains dependent on invasive procedures. Histological examination remains the standard for diagnosis, whereas immunohistochemical and genetic tests are utilized for treatment decisions and prognosis determinations. Therefore, we conducted a comprehensive review of literature published in PubMed on breast cancer biomarkers between 2009 and 2013. The keywords that were used together were breast cancer, biomarkers, diagnosis, prognosis and drug response. The cited references of the manuscripts included in this review were also screened. We have comprehensively summarized the performance of several biomarkers for diagnosis, prognosis and predicted drug responses of breast cancer. Finally, we have identified 15 biomarkers that have demonstrated promise in initial studies and several miRNAs. At this point, such biomarkers must be rigorously validated in the clinical setting to be translated into clinically useful tests for the diagnosis, prognosis and prediction of drug responses of breast cancer.

Expression of epithelial-mesenchymal transition markers at the invasive front of oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is one of the most common malignances. In epithelial-mesenchymal transition (EMT), epithelial cells switch to mesenchymal-like cells exhibiting high mobility. This migratory phenotype is significant during tumor invasion and metastasis. Objective : The aim of this study is to evaluate the expression of the EMT markers E-cadherin, N-cadherin and vimentin in OSCC. Material and Methods : Immunohistochemical detection of E-cadherin, N-cadherin and vimentin was performed on 20 OSCC samples. Differences in the expression of each protein at the invasive front (IF) and in the central/superficial areas (CSA) of the tumor were assessed. Differences in the expression of each protein at the IF of both histologically high- and low-invasive OSCCs were evaluated. Associations among expression of proteins at the IF were assessed. Correlations between the expression levels of each protein at the IF and the tumor stage and clinical nodal status were also evaluated. Results : Reduced expression of E-cadherin was detected in 15 samples (75%). E-cadherin expression was reduced at the IF when compared to the CSA and in high-invasive tumors when compared to low-invasive tumors. All samples were negative for N-cadherin, even though one sample showed an inconspicuous expression. Positive expression of vimentin was observed in 6 samples (30%). Nevertheless, there was no difference in vimentin expression between the IF and the CSA regions or between the low- and high-invasive tumors. Furthermore, no association was observed among protein expression levels at the IF. Finally, no correlations were observed between each protein’s expression levels and tumor stage or clinical nodal status. Conclusions : Reduced E-cadherin expression at the IF and its association with histological invasiveness suggest that this protein is a noteworthy EMT marker in OSCC. Although vimentin was also detected as an EMT marker, its expression was neither limited to the IF nor was it related to histological invasiveness.

Assessment of angiogenesis by CD105 antigen in epithelial salivary gland neoplasms with diverse metastatic behavior

BackgroundInformation on the biology of metastasis development in salivary gland tumors is scarce. Since angiogenesis seems associated with this phenomenon in other tumors, we sought to compare salivary gland tumors with diverse metastatic behavior in order to improve the knowledge and management of these lesions.MethodsSamples from the most important salivary gland tumors were segregated according to its metastatic behavior and submitted to routine immunohistochemistry to identify vessels positive for CD105 expression. Frequency of positive cases and intratumoral microvessel density (IMD) was compared among the group of lesions.ResultsCD105 positive vessels were absent in normal salivary gland tissue, were rare in pleomorphic adenomas and adenoid cystic carcinomas (ACC), more common in polymorphous low-grade adenocarcinomas and highest in mucoepidermoid carcinomas. Only ACC with such feature were metastatic. IMD was higher in malignant rather than benign tumors.ConclusionImmunostaining of CD105 in salivary gland tumors implies participation of angiogenesis in the development of malignant lesions, as well as some role for myoepithelial cells in the control of new vessel formation. In addition, suggest that ACC with positive CD105 vessels are at higher risk for metastasis.

Paracoccidioidomycosis: a series of 66 patients with oral lesions from an endemic area

Paracoccidioidomycosis (PCM) is the most important systemic mycosis in Latin America. It has been regarded as a multifocal disease, with oral lesions as the prominent feature. To provide useful information concerning the diagnosis and management of the disease, this study describes demographic and clinical data from the medical records of a consecutive series of 66 Brazilian patients from an endemic area, evaluated in a referral centre for oral diagnosis. In this sample of patients, there was a predominance of middle‐aged male patients, who were primarily rural workers. Chronic multifocal disease was prevalent, with lesions also detected in the lungs, lymph nodes, skin or adrenal glands. Most of the cases presented with lesions at the gingival mucosa followed by the palate and lips; these conditions occurring in the oral cavity were frequently associated with pain. Importantly, most of the patients sought professional care for oral lesions. The diagnosis was obtained through exfoliative cytology and/or biopsy of the oral lesions. Medical treatment was effective, and there were no mortalities in the sample. The present findings not only confirm the importance of oral lesions in the diagnosis and management of PCM but also illustrate that questions still remain unclear, such as the possibility of direct inoculation of the fungus onto oral tissues.

Giant Leiomyomatous Hamartoma of the Tongue

t U f r b u s i o p amartoma has been defined as a focal benign tumorike mass composed of a disordered mixture of maure tissues that normally occur in the affected part, ut with predominance of one particular tissue to this rea. Clinically, these lesions grow in concert with he patient and therefore do not show any tendency or uncontrolled growth. In oral tissues, hamartomas omposed of blood or lymphatic vessels (hemangioas and lymphangiomas) are relatively common. hese are usually single lesions in otherwise healthy atients, while there are eventual reports of associaion with congenital developmental defects such as

Cervical Castleman's Disease in Childhood

Castleman’s disease (CD) is an uncommon benign non-neoplastic lymphoproliferative disease. It was first described by Castleman and colleagues in 2 different papers, which described progressive enlargement of the mediastinal lymph nodes. 1,2 The etiology and pathogenesis of CD remains to be established. Different hypotheses, such as chronic inflammatory process associated or not to viral infection, angiolymphoid hamartomatous or choristomatous process, immunologic disturbance, and neoplastic transformation have been raised to explain it. 3,4 Recently, a unifying model of pathogenesis has implicated human herpes virus-8-stimulated interleukin-6 production by B-cell mantle zone. In turn, IL-6 would induce vascular endothelial growth factor production and B-cell proliferation, resulting in an increased vascularization and cellularity in the affected lymph nodes. 4

Vascular endothelial growth factor and thymidine phosphorylase expression in salivary gland tumors with distinct metastatic behavior

BACKGROUND Metastasis of salivary gland tumors has a negative impact on survival. Angiogenesis and its factors are potential markers for predicting metastasis in different malignant tumors, but this is not the case for salivary gland tumors. METHODS Salivary gland tumors of distinct biologic behavior were analyzed according to the semiquantitative immunoexpression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP). RESULTS Vascular endothelial growth factor expression was predominantly weak in benign tumors. Weak TP expression was observed in 100% cases of benign tumors and in 74.3% of primary malignant tumors. High VEGF and TP expression levels were significantly associated with primary malignant tumors but not with primary non-metastasizing and primary metastasizing malignant tumors or with subtypes of malignant tumors. CONCLUSIONS Vascular endothelial growth factor and TP expression levels discriminate benign and malignant tumors but cannot predict metastasis from non-metastasizing tumors.

Multicentric granular cell tumor: report of a patient with oral and cutaneous lesions

Granular cell tumor (GCT) is an uncommon benign neoplasm of soft tissue that characteristically affects the oral cavity, with increased frequency in the tongue. In this paper, we report a multicentric GCT affecting a 41-year-old black woman, with nodules in perineum, groin, vulva, tongue and lip. Some of these lesions were surgically resected, but in a six-year follow-up, new primary lesions and recurrences were observed. In addition, the patient opted to do not remove some of these lesions, but there were not significant intercurrences. In view of the present findings, aspects related to clinical presentation, multiplicity, malignant potential, and treatment of GCT are discussed.

Adenoid cystic carcinoma of the salivary gland: a clinicopathological study of 49 cases and of metallothionein expression with regard to tumour behaviour

Adenoid cystic carcinoma (AdCC) of the salivary glands shows heterogeneous behaviour, with metastasis as a key indicator of poor prognosis. Metallothionein (MT) expression has been associated with poor prognosis of diverse neoplasms. We evaluated prognostic factors for AdCC and the role played by MT, focusing on metastatic behaviour.

Warthin's tumor at the Brazilian National Cancer Institute: additional evidence of homogeneous sex prevalence and association with other neoplasms.

Purpose of the Study: To report the largest Brazilian series of Warthin’s tumor (WT). Procedures: The medical files of 76 patients with WT treated in the Brazilian National Cancer Institute from 1996 to 2006 were reviewed. Results: The male:female ratio was 2:1, with a predominance of white, old, and smoking patients. However, there were more women among the nonsmokers. One fifth of the patients presented with synchronous multiple lesions. Parotid lesions were prevalent, but there were patients with lesions in cervical lymph nodes and in the inferior lip. Most cases were treated by superficial parotidectomy, without recurrences. One fourth of the patients also developed other primary neoplasms. Conclusions: The observed data do not differ from those in the international literature. Multiplicity and the development of other neoplastic diseases require close clinical management of patients with WT. Message: The previously unreported observation of female prevalence among nonsmoking people with WT should be confirmed and explored in future studies.