Role of cytochrome P-450 genetic polymorphisms in oral carcinogenesis.

Oral cancer is one of the most frequent head and neck cancers, and epidemiological studies have shown that smoking is a major risk factor in this pathology. However, as not all smokers develop oral cancer, some individuals must be more susceptible to develop this disease. This individual susceptibility has been related to different genetic variants in metabolizing enzymes. The cytochrome P-450 (CYP) family of enzymes metabolizes tobacco-related carcinogens producing reactive metabolites, which could cause DNA damage. Because of their functional role in the metabolism of tobacco-related compounds, the genetic polymorphisms found in the genes that code for CYP enzymes have been suggested to modulate oral cancer risk and contribute to individual susceptibility. In this review, we analyze and update the available evidence in the literature regarding the polymorphisms of CYP genes in relation to the susceptibility of developing oral cancer.

Overexpression of cyclooxygenase-2 as a biomarker in different subtypes of the oral lichenoid disease.

OBJECTIVE: Oral lichenoid disease (OLD) includes a number of chronic inflammatory processes including oral lichen planus (OLP) and oral lichenoid lesions (OLL) with controversial diagnosis and prognosis. Cyclooxygenase-2 (COX-2) is a key enzyme for inflammatory processes and cellular proliferation. Its overexpression in some premalignant chronic inflammatory diseases and malignant neoplasias could point to its potential as a prognostic factor. The aim of this study was to analyze the COX-2 expression in different subtypes of OLD because of its potential to be a marker of altered behavior. STUDY DESIGN: Forty-four samples from OLD patients were studied (30 females and 14 males) and classified according to their clinical (C1: only papular lesions/C2: papular and other lesions) and histological features (HT: OLP typical/HC: OLP compatible) according to published criteria. Standard immunohistochemical procedure was performed for COX-2 expression and a comparative and descriptive statistical analyses were performed. RESULTS: Epithelial COX-2 overexpression was observed in 24 (54.5%) cases (C1: 13 [54.2%]/C2: 11 [45.8%], HT: 9 [37.5%]/HC: 15 [62.5%], P = .032). Inflammatory COX-2 overexpression was observed in 14 (31.8%) cases (C1: 6 [42.9%]/C2: 8 [57.1%], HT: 4 [28.6%]/HC: 10 [71.4%], P = .032). CONCLUSION: Differences in COX-2 expression in subtypes of OLD may distinguish cases with a higher premalignant potential.

Oral cancer and polymorphism of ethanol metabolising genes.

Oral cancer is the sixth most common cancer worldwide and a major health problem in some parts of the world. Epidemiological studies have shown that habitual alcohol consumption could be a risk factor in oral carcinogenesis, although the true involvement of alcohol is unknown. Via alcohol dehydrogenase (ADH) and cytochrome P450 oxidase (CYP) alcohol is metabolized to acetaldehyde, a highly toxic compound, which plays an important role in carcinogenesis. Subsequently, and during the metabolizing process, acetaldehyde becomes acetate by acetaldehyde dehydrogenase (ALDH). Therefore, acetaldehyde levels are determined mainly by the action of ADH, CYP and ALDH. Recently, several studies have found that certain polymorphisms of genes encoding these enzymes confer a higher or lower metabolic activity and therefore different risk for certain malignancies such as oral cancer. In this review, we analyze the polymorphisms of alcohol metabolising enzymes in relation susceptibility to an oral cancer.

Immunoexpression of p53, Ki-67 and E-cadherin in basaloid squamous cell carcinoma of the larynx.

INTRODUCTION: Basaloid is a rare and poorly-differentiated variant of squamous cell carcinoma of the larynx, with an invasive solid growth of cells in a lobular configuration. Different molecular markers, such as p53, Ki-67 and E-cadherin, have been shown to be prognostic factors in head and neck cancer. OBJECTIVE: To evaluate the relationship between the immunoexpression of p53, Ki-67 and E-cadherin in relation to prognosis in basaloid squamous cell carcinoma of the larynx (BSCCL). PATIENTS AND METHODS: We retrospectively studied 11 cases of BSCCL, all male with a mean age of 62.4 years. Immunohistochemical analyses were performed on paraffin-embedded tissues using p53 (DO- 7), Ki-67 (MIB-1) and E-cadherin (36B5) antibodies. Quantitative assessments of the expression and descriptive statistical analyses were performed. RESULTS: In 72.7% of the cases, clinically advanced stages III-IV were diagnosed. Average survival time was 56.09 months, and 72.7% of patients died as a consequence of the tumour. Immunoreactivity of p53 (>10% of cells) was detected in the 81.8% of the cases. The 72.7% of the cases showed overexpression of Ki-67 (>50% of cells). The cases with low immunoexpression of Ki-67 and p53 had the best clinicopathological data. All cases showed a decreased expression of E-cadherin. CONCLUSIONS: BSCCL is an aggressive variant of the squamous cell carcinoma and has a high expression of p53 and Ki-67 with a low expression of Ecadherin. These results could be related to the aggressiveness of the disease and its poor prognosis.

Immunoexpression of p53, Ki-67 and E-cadherin in basaloid squamous cell carcinoma of the larynx

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Introduction. Basaloid is a rare and poorly-differentiated variant of squamous cell carcinoma of the larynx, with an invasive solid growth of cells in a lobular configuration. Different molecular markers, such as p53, Ki-67 and E-cadherin, have been shown to be prognostic factors in head and neck cancer. Objective. To evaluate the relationship between the immunoexpression of p53, Ki-67 and E-cadherin in relation to prognosis in basaloid squamous cell carcinoma of the larynx (BSCCL). Patients and methods. We retrospectively studied 11 cases of BSCCL, all male with a mean age of 62.4 years. Immunohistochemical analyses were performed on paraffin-embedded tissues using p53 (DO- 7), Ki-67 (MIB-1) and E-cadherin (36B5) antibodies. Quantitative assessments of the expression and descriptive statistical analyses were performed. Results. In 72.7% of the cases, clinically advanced stages III-IV were diagnosed. Average survival time was 56.09 months, and 72.7% of patients died as a consequence of the tumour. Immunoreactivity of p53 (>10% of cells) was detected in the 81.8% of the cases. The 72.7% of the cases showed overexpression of Ki-67 (>50% of cells). The cases with low immunoexpression of Ki-67 and p53 had the best clinicopathological data. All cases showed a decreased expression of E-cadherin. Conclusions. BSCCL is an aggressive variant of the squamous cell carcinoma and has a high expression of p53 and Ki-67 with a low expression of Ecadherin. These results could be related to the aggressiveness of the disease and its poor prognosis