André L Vettore

Publications (49) View all

• Article: Evaluation of the methylation profile of exfoliated cell samples from head and neck squamous cell carcinoma patients.

  Ana Luiza Bomfim Longo, Marianna M Rettori, Ana Carolina de Carvalho, Luiz Paulo Kowalski, André Lopes Carvalho, André Luiz Vettore
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  ABSTRACT: Background: Silencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. The aims of this study were to determine the methylation profile of exfoliated tumors cells collected from head and neck squamous cell carcinoma (HNSCC) patients and to evaluate its prognostic significance. Methods: The methylation profile and level of a 20 genes-panel were evaluated by QMSP in exfoliated tumor cell samples from 96 HNSCC patients. Results: CCNA1 (60.4%), DCC (54.2%) and TIMP3 (35.4%) were frequently methylated in these samples. Patients with exfoliated tumors cells positive for DCC methylation showed a trend toward a lower local recurrence-free survival.. Conclusions: These findings indicate that a low invasive method could be used to access the methylation profile of exfoliated cells from HNSCC patients. Moreover, our data provide evidence that hypermethylation of DCC could be useful as prognostic indicator for this malignance. Head Neck, 2013.
  Head & Neck 04/2013; · 2.40 Impact Factor
• Article: Prognostic Significance of TIMP3 Hypermethylation in Post-treatment Salivary Rinse from Head and Neck Squamous Cell Carcinoma Patients.

  Marianna M Rettori, Ana Carolina de Carvalho, Ana Luiza Bomfim Longo, Cleyton Zanardo de Oliveira, Luiz Paulo Kowalski, André Lopes Carvalho, André Luiz Vettore
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  ABSTRACT: Hypermethylation in the promoter regions of genes is associated with suppression of gene expression and has been considered a potential molecular marker for several tumor types, including Head and Neck Squamous Cell Carcinomas (HNSCC). Moreover, hypermethylation can be detected in body fluids such as saliva and can be useful for the diagnosis and prognosis of patients suffering from cancer. To evaluate the hypermethylation profile as a tool for early detection of tumor recurrences, this study determine the methylation status of 24 genes in salivary rinses collected from HNSCC patients at diagnosis, just after the last curative treatment and in the patients' follow up visit at six months after treatment. In the analysis of salivary rinse samples taken at diagnosis of HNSCC patients, 5 genes (CCNA1, DAPK, DCC, MGMT and TIMP3) showed high specificity and sensitivity. Hypermethylation in any of these five genes was correlated with the presence of tumors in the oral cavity. Patients with TIMP3 methylation in samples collected six months after the last curative treatment had lower local recurrence-free survival (p = 0.008). Multivariate analysis confirmed that this hypermethylation pattern remained as an independent prognostic factor for local recurrence (p = 0.025). This study presents, for the first time, the detection of TIMP3 promoter hypermethylation in post-treatment salivary rinse as an independent prognostic maker for local recurrence-free survival in patients with HNSCC, justifying the use of DNA hypermethylation detection in saliva as a tool for identifying and monitoring HNSCC patient's subgroups with high risk of developing local recurrence.
  Carcinogenesis 10/2012; · 5.70 Impact Factor
• Article: Identification of upregulated genes in oral squamous cell carcinomas.

  Roberta C Lessa, Antonio Hugo J F M Campos, Carlos Elias de Freitas, Felipe Rodrigues da Silva, Luiz Paulo Kowalski, André Lopes Carvalho, André Luiz Vettore
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  ABSTRACT: BACKGROUND: Oral cancer is the most common subset of head and neck squamous cell carcinomas (HNSCC). These tumors often have an aggressive clinical outcome hallmarked by a propensity for local invasion and regional nodal metastasis. Upregulated genes could be useful as markers for diagnosis, prognosis, and as new drug targets for these tumors. METHODS: To identify upregulated genes in oral squamous cell carcinomas (OSSCs), we examined the ORESTES public database and used a quantitative reverse transcription-polymerase chain reaction (qRT-PCR) approach to determine the expression level of selected genes in tumor samples. RESULTS AND CONCLUSIONS: The ORESTES data mining analysis indicated 40 upregulated genes in HNSCC. Nine of these candidate genes were selected for further qRT-PCR validation and 3 of them (ALDOA, AHSA1, and POLQ) were frequently found upregulated in OSCC samples, which may indicate an association of these genes with the carcinogenesis process in this tumor site and they can constitute potential new targets for therapy. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.
  Head & Neck 09/2012; · 2.40 Impact Factor
• Article: Clinical significance of molecular alterations in histologically negative surgical margins of head and neck cancer patients.

  Ana Carolina de Carvalho, Luiz Paulo Kowalski, Antônio Hugo José Fróes Marques Campos, Fernando Augusto Soares, André Lopes Carvalho, André Luiz Vettore
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  ABSTRACT: The development of locoregional recurrence is the main reason for treatment failure in head and neck squamous cell carcinomas (HNSCC) and the remaining of tumor cells in surgical margins is associated with recurrence. Surgical margins are considered negative based on histologic assessment of the pathological specimen. However, this method lacks sensitivity in identifying cells that already started malignant transformation but have not yet developed a pathologic phenotype. We investigated the usefulness of assessing the expression of PTHLH, EPCAM, MMP9, LGALS1 and MET for the detection of molecular alterations in histologically negative surgical margins and determine the correlation of these tumor-related alterations with clinical and prognostic parameters. Differential gene expression was determined by quantitative RT-PCR analyses in normal mucosa, HNSCC and negative margin samples. Thirty-eight percent of the histologically negative surgical margins examined were margin-positive for overexpression of at least one of the genes evaluated. Moreover, MMP9 and PTHLH overexpression in the surgical margins was associated with the development of second primary tumors (p=0.002) and lower rates of local control (log rank test p=0.022; HR=4.186; p=0.035), respectively. These findings demonstrate that the overexpression of tumor-related genes in histologically negative surgical margins is a frequent event. The use of qRT-PCR may be an useful tool in detecting actually negative HNSCC surgical margins and the overexpression of specific genes in these margins could be helpful in the identification of patients with a higher risk of developing second primary tumors and local recurrences, thus aiding the surgeon in the delineation of the HNSCC resection extent and helping in the planning of adjuvant therapy.
  Oral Oncology 11/2011; 48(3):240-8. · 2.86 Impact Factor
• Article: Claudin-7 down-regulation is an important feature in oral squamous cell carcinoma.

  Silvia Vanessa Lourenço, Cláudia Malheiros Coutinho-Camillo, Marcilei Elisa Cavicchioli Buim, Ana Carolina de Carvalho, Roberta Cardim Lessa, Cláudia Maria Pereira, André Luiz Vettore, André Lopes Carvalho, José Humberto Fregnani, Luiz Paulo Kowalski, Fernando Augusto Soares
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  ABSTRACT: Claudins, a large family of essential tight junction (TJ) proteins, are abnormally regulated in human carcinomas, especially claudin-7. The aim of this study was to investigate claudin-7 expression and alterations in oral squamous cell carcinoma (OSCC). Expression of claudin-7 was analysed in 132 cases of OSCC organized in a tissue microarray. Claudin-7 mRNA transcript was evaluated using real-time polymerase chain reaction and the methylation status of the promoter was also assessed. Claudin-7 was negative in 58.3% of the cases. Loss of claudin-7 protein expression was associated with recurrence (P = 0.019), tumour size (P = 0.014), clinical stage of OSCC (P = 0.055) and disease-free survival (P = 0.015). Down-regulation of the claudin-7 mRNA transcripts was observed in 78% of the cases, in accordance with immunoexpression. Analysis of the methylation status of the promoter region of claudin-7 revealed that treatment of O28 cells (that did not express claudin-7 mRNA transcripts) with 5-Aza-2'-Deoxycytidine (5-Aza-dC) led to the re-expression of claudin-7 mRNA transcript. Loss of claudin-7 expression is associated with important subcellular processes in OSCC with impact on clinical parameters.
  Histopathology 11/2010; 57(5):689-98. · 3.08 Impact Factor