Edilmar De Moura Santos

Distribution of Hypoxia-Inducible Factor-1α and Glucose Transporter-1 in Human Tongue Cancers

PURPOSE Oral squamous cell carcinomas have the potential for rapid and unlimited growth. Therefore, hypoxic tissue areas are common in these malignant tumors and contribute to cancer progression, therapy resistance, and poor outcomes. The aim of the present study was to analyze the gene product distribution of hypoxia-inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) in cases of tongue squamous cell carcinoma (TSCC) and to identify a preliminary correlation between these proteins and clinical staging and Bryness histologic grading system (HGS). MATERIALS AND METHODS The sample included 57 cases of TSCC. Histologic sections of 3 μm were submitted to the immunoperoxidase method and semiquantitative analysis. The association between HIF-1α and GLUT-1 expression in TSCC and the clinical stage and the HGS of Bryne (1998) was evaluated using the χ(2) test, with the significance level set at 0.05 (α = 0.05). RESULTS HIF-1α was mainly expressed in the nucleus/cytoplasm of neoplastic cells, most specimens exhibited diffuse staining in neoplastic cells (84.2%), and focal staining was only observed in perinecrotic areas (15.8%). GLUT-1 was expressed in the cytoplasm and membrane of malignant cells, and diffuse staining was observed in all cases. The intensity of HIF-1α expression correlated significantly with clinical stage (P = .011) and HGS (P = .002). A significant association was observed between the distribution of HIF-1α expression and metastasis (P = .040). Immunoexpression of GLUT-1 correlated significantly with clinical stage (P = .002) and HGS (P = .000). GLUT-1 expression in the peripheral island was predominant in most low-grade tumors (78.6%); in the high-grade cases, the expression prevailed in the location center/periphery (55.8%). Comparison of the location of the tumor island in the different histologic grades showed a statistically significant difference (P = .025). CONCLUSION The expression of HIF and GLUT proteins within TSCC appears to be associated with disease stage, grade, and the presence of metastases. Additional studies are needed to evaluate the diagnostic and prognostic uses of these proteins in the treatment of TSCC.

DNA base excision repair proteins APE-1 and XRCC-1 are overexpressed in oral tongue squamous cell carcinoma

BACKGROUND DNA repair systems play a critical role in protecting the human genome from damage caused by carcinogens. Modifications in DNA repair genes may be responsible for tumor development and resistance of malignant cells to chemotherapeutic agents. The major pathway for oxidative DNA damage repair is the base excision repair pathway. This study aimed to assess the immunoexpression of DNA repair proteins APE-1 and XRCC-1 and its association with clinical, histologic, and survival parameters in oral tongue squamous cell carcinoma, to investigate a possible role for those proteins in tumor behavior. METHODS The expression of APE-1 and XRCC-1 was evaluated by immunohistochemistry in 82 cases of oral tongue squamous cell carcinoma. Histopathological grading was performed for each case. Pearsons chi-square and Fishers exact tests were used to determine the association between protein expressions and clinicopathological features of tumors, whereas Kaplan-Meier curves and Cox regression were used to analyze disease-specific and disease-free survival. Statistical significance was set at P ≤ 0.05. RESULTS APE-1 was highly expressed in the nucleus and cytoplasm in 64.6% of cases, and XRCC-1 showed overexpression only in the nucleus in 61% of cases. High expression of XRCC-1 was significantly associated with tumors at early clinical stages (I and II, P < 0.01) and nodal status (P = 0.03). Both proteins were not associated with other clinical parameters, histopathological grading, or survival. CONCLUSIONS DNA base excision repair proteins APE-1 and XRCC-1 are upregulated in oral tongue squamous cell carcinoma, and XRCC-1 expression is associated with better clinical staging and nodal status.

Primary Adenocarcinoma of the Colon with Metastases to the Mandible and Liver: A Case Report

Metastatic lesions to the mandible may be originated from primary tumors elsewhere in the body. However, metastatic colonic carcinomas to this bone have been described infrequently. We report the case of a 71-year-old man with an adenocarcinoma in the sigmoid colon with liver metastasis. The patient underwent chemotherapy with indication of sigmoidectomy and retroperitoneal lymphadenectomy. One year and four months after the first metastatic diagnosis, the patient presented a tumor mass in the body and branch of the right mandible. Histopathological and immunohistochemical analysis with monoclonal antibodies specific for CEA, CK20, CDX-2, and vilin were compatible with the diagnosis of moderately differentiated metastatic adenocarcinoma with colonic origin. However, due to the wide spread of the disease, the patient died four months later. Tumor markers have been applied in clinical practice to assist in the diagnosis and to help guide prognosis, staging and treatment of cancer. The management of metastatic lesions remains a controversial issue and the development of new and more specific markers of gastrointestinal differentiation that may promote early diagnosis, are of continuous interest.

Clinicopathological significance of SNPs in RAD51 and XRCC3 in oral and oropharyngeal carcinomas

BACKGROUND This study investigated the influence of single nucleotide polymorphisms (SNP) in RAD51 and XRCC3 on susceptibility to oral and oropharyngeal squamous cell carcinomas (SCC) and determined their clinicopathological significance. SUBJECTS AND METHODS SNPs rs1801320 and rs1801321 in RAD51 and rs861539 in XRCC3 were genotyped in 81 patients presenting oral SCC, 45 presenting oropharyngeal SCC, and 130 healthy controls, using TaqMan allelic discrimination assays. Multiple logistic regression models were used to explore the association between SNPs and cancer development, as well as gene-gene (GxG) interaction and gene-environmental factor (GxE) interaction. Clinicopathological associations were verified through the chi-square test, and univariate and multivariate methods were applied for survival analyses. RESULTS Although allelic and genotypic models and the GxG interaction analysis were nonsignificant, the GxE analysis revealed synergistic effects of the risk alleles of rs1801320, rs1801321, and rs861539 with smoking and alcohol consumption on susceptibility to oral and oropharyngeal SCC. Furthermore, oropharyngeal SCC patients carrying the XRCC3 rs861539 GT/TT genotype (T risk allele) presented a shorter overall survival than GG genotype carriers. CONCLUSION Combined effects of RAD51 (rs1801320 and rs1801321) and XRCC3 (rs861539) SNPs with environmental carcinogens (tobacco and alcohol) are associated with oral and oropharyngeal SCC development.

Clinicopathological evaluation and survival of patients with squamous cell carcinoma of the tongue

Background Early detection of oral cancer is the most effective means of reducing morbidity, complexity, and extent of treatment. This study evaluated the clinicopathological profile of epidermoid carcinoma of the tongue, including treatment and survival. Material and Methods This observational, retrospective cross-sectional study evaluated patients with squamous cell carcinoma of the tongue treated at the Dr. Luiz Antônio Hospital, Natal, Brazil, from January 2001 to December 2011. Survival variables were calculated using the Kaplan-Meier method and compared by log rank tests. Results Of the 412 patients diagnosed in this period, 298 (72.3%) were men; their mean age was 60.5 years, and 69.2% were diagnosed with stage III/IV tumours. Improved survival was associated with early stage diagnosis, absence of affected lymph nodes at diagnosis, and treatment with surgery alone. Conclusions Late stage diagnosis of oral cancer negatively affects patient survival. In addition, the general public should be made aware of the prognostic factors for oral SCC of the tongue and of the importance of periodic examinations of the oral cavity. Key words:Mouth neoplasms, tongue neoplasms, carcinoma, squamous cell, survival analysis.

Hallazgo Incidental de Carcinoma de Células Acinares de la Mucosa Oral con Carcinoma Adenoide Quístico Metacrónico del Labio Superior

Multiple salivary gland tumors represent an unusual event characterized by the development of composite lesions originated from minor or major salivary glands. These neoplasms can be categorized into three perspectives: Histologic type, time of appearance and topographic distribution. We report an unusual case of a 73-year-old black man with an acinic cell carcinoma (ACC) of the oral mucosa discovered incidentally during surgical removal of an adjacent mucocele. Approximately one year after the first consultation, the patient was seen at the local cancer reference center with a third lesion that was diagnosed as an adenoid cystic carcinoma (AdCC) of the upper lip. The patient underwent surgical reconstruction of the treated areas and has been free of the disease for the past year. To our knowledge, the combination of ACC and AdCC in intraoral sites has not been reported in the literature.