ABSTRACT
To evaluate molecular epithelial changes, we investigated whether a profile of survivin, cyclin dependent kinase inhibitor 2A (CDKN2A), epidermal growth factor receptor (EGFR), polo like kinase 1 (PLK1), p63, p40 (Δnp63 isoform), cyclin D1 (CCND1) and BCL2 apoptosis regulator (BCL2) proteins could predict malignant transformation. Different tissue segments (tumor adjacent epithelium; dysplasia and tumor) from a total of 109 patients were analyzed by immunohistochemistry. An increased expression of survivin (p < 0.001), PLK1 (p = 0.001), and p63 (p < 0.001) in parallel to reduced immunostaining of p40 (p < 0.001) and BCL2 (p = 0.029) was observed among the tissue segments analyzed. Our study revealed that survivin, PLK1, p63, p40 and BCL2 play a role in oral tumorigenesis and represent promising biomarkers able to recognize mesenchymal phenotype induction in the transition from nonmalignant cells to tumor cells. These results reveals critical interaction between survivin, PLK1, p63, p40 promising proteins during invasive carcinoma development.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Mouth Mucosa/metabolism , Mouth Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/pathology , Cell Cycle Proteins/metabolism , Cell Transformation, Neoplastic/pathology , Cyclin D1/metabolism , Cyclin-Dependent Kinase Inhibitor p16/metabolism , ErbB Receptors/metabolism , Female , Humans , Immunohistochemistry , Male , Middle Aged , Mouth Neoplasms/pathology , Protein Isoforms , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Survivin/metabolism , Transcription Factors/metabolism , Polo-Like Kinase 1ABSTRACT
Squamous cell carcinoma of the oral cavity and oropharynx is the sixth most common type of cancer in the world. During tumorigenesis, gene promoter hypermethylation is considered an important mechanism of transcription silencing of tumor suppressor genes, such as DAPK, MGMT and RUNX3. These genes participate in signaling pathways related to apoptosis, DNA repair and proliferation whose loss of expression is possibly associated with cancer development and progression. In order to investigate associations between hypermethylation and clinicopathological and prognostic parameters, promoter methylation was evaluated in 72 HPV negative oral and oropharyngeal tumors using methylation-specific PCR. Hypermethylation frequencies found for DAPK, MGMT and RUNX3 were 38.88%, 19.44% and 1.38% respectively. Patients with MGMT hypermethylation had a better 2-year overall survival compared to patients without methylation. Being MGMT a repair gene for alkylating agents, it could be a biomarker of treatment response for patients who are candidates for cisplatin chemotherapy, predicting drug resistance. In view of the considerable levels of hypermethylation in cancer cells and, for MGMT, its prognostic relevance, DAPK and MGMT show potential as epigenetic markers, in a way that additional studies may test its viability and efficacy in clinical management.
ABSTRACT
OBJECTIVE: The aim of this study was to evaluate the application of in situ hybridization using E6/E7 mRNA probes to identify the frequency of high-risk HPV transcriptionally active and the use of HPV status as a prognostic biomarker in oral cavity squamous cell carcinoma (OCSCC). METHODS: Ninety-nine OCSCC samples were evaluated from Hospital Santa Rita de Cassia, Hospital Universitário Cassiano Antônio de Moraes and University Hospitals Coventry and Warwickshire NHS Trust. After tissue microarray construction, the slides were submitted to an in situ hybridization detection method for HPV E6/E7 mRNA. HPV status was designated a binary classification. Multiple logistic regression examined the association of HPV with clinical features and other risk factors, using SPSS® software. For all hypothesis tests, a significance level of pâ¯≤â¯0.05 was considered. RESULTS: HPV frequency in oral squamous cell carcinoma was 8%. There was no association between HPV and clinical variables and between the main prognostic features and known risk factors. There was no difference in the prevalence of HPV for oral cavity squamous cell carcinoma by geography (Brazil vs UK). CONCLUSIONS: A low frequency of E6/E7 mRNA by RNA in situ hybridization was found in oral cavity squamous cell carcinoma, which supports the evidence that HPV-driven cancer of the oral cavity is uncommon.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Papillomaviridae , Papillomavirus Infections , RNA, Messenger , Brazil , Head and Neck Neoplasms/virology , Humans , In Situ Hybridization , Papillomaviridae/pathogenicity , Papillomavirus Infections/diagnosis , RNA, ViralABSTRACT
As mucoceles säo lesoes benígnas raras dos seios paranasais. O seio frontal é o mais freqüentemente afetado sendo sua manifestaçäo clínica mais usual a proptose e diplopia. A tomografia computadorizada e a ressonância nuclear magnética säo os exames radiológicos de escolha para o diagnóstico desta lesäo. O objetivo do tratamento é a ressecçäo completa da lesäo cística com ampla comunicaçäo com a cavidade nasal. Os autores apresentam um caso raro de mucocele frontal avançado com ênfase aos padröes clínicos e o tratamento cirúrgico nao convencional da doença.
