Connexin 43, Bcl-2, Bax, Ki67, and E-cadherin patterns in oral squamous cell carcinoma and its relationship with GJA1 rs12197797 C/G

Background: To our knowledge, there is no useful and accurate prognostic biomarker or biomarkers for patientswith oral squamous cell carcinoma (OSCC), a tumor with uncertain biological behavior, and unpredictable clinical progress. The purposes of this study were: a) to determine the expresión profile of Connexin 43, Bcl-2, Bax,E-cadherin, and Ki67 in patients with OSCC; b) identify the GJCA1 rs12197797 genotypic composition.Material and Methods: A cross-sectional study using genomic DNA and biopsy samples extracted from the oralmucosa with/without OSCC, older than 18 years, both genders, attended at Facultad de Odontología, UniversidadNacional Córdoba. Immunostaining for Cx43, Bcl-2, Bax, E-cadherin, and Ki67 and genotyping GJA1 rs12197797by RFLP were performed. Odds Ratio (95% CI), Spearman Coefficient were estimated. Mann-Whitney test wasapplied to analyze immunostaining between controls/cases (p <0.05 was set for statistical significance).Results: GG (mutant) was the most frequent genotype in patients with OSCC diagnosis (53.2%) in relation toCC “healthy” genotype (p=0.00487; OR=7.33; CI95% [1.1-54.7]). And, the allele G (mutant) had a presence in75.5% of OSCC patients. However, no significant association was observed between alleles C/G and diagnosis(p=0.0565). The heterozygous genotype was the most frequent in the patients of both groups Cx43 and E-cadherinmarkers were lower in OSCCs in relation to controls. Ki67 and Bcl-2 immunolabeling were high on OSCC, andBax immunomarker was diminished in OSCC.Conclusions: We hypothesized that the oral epithelium losses Connexin 43 and E-cadherin in the membrane, whichmodifies cell differentiation. The Ki67 and Bcl2 overexpression would increase the cell density in the tissue, by promoting proliferation and decreasing apoptosis. And, this study shows evidence that patients who carry on allele G ofGJA1rs12197797 could be at risk of developing OSCC. (AU)

DNA repair, NFKß, and TP53 polymorphisms associated with potentially malignant disorders and oral squamous cell carcinoma in Argentine patients.

OBJECTIVE: An important strategy in cancer prevention is to identify individual susceptibilities for cancer development through the genomic profile. Developing countries such as Argentina have no data on genetic composition. The aim of this study was to evaluate the single nucleotide polymorphisms of genes related to DNA repair (XCCR3, XPD), cell cycle arrest/apoptosis (TP53), and inflammation (NFKß) of patients with precancer and oral cancer and to contribute to recognizing potential risk of developing these pathologies, and incorporate the risk patients into a clinical follow-up program in Córdoba, Argentina. STUDY DESIGN: A cross-sectional study was performed on 140 patients with oral squamous cell carcinoma (OSCC), oral potentially malignant disorders (OPMDs), and controls. Genotyping of single nucleotide polymorphisms was performed using allele-specific polymerase chain reaction or restriction fragment length polymorphism techniques. The variables were evaluated by bivariate and multivariate statistical methods, with P < .05 statistically significant. RESULTS: The multiple correspondence analyses showed that patients with OSCC are clustered with the T allele of XRCC3 T241 M and the C allele of TP53 R72 P, and patients with OPMDs are clustered with the T allele of NFKß-519. CONCLUSION: Our preliminary results showed that the C allele of the Pro72 variant of TP53 was related to OSSC and OPMD, and the T allele of NFKß-519 is related to OPMDs in Argentine patients.

Study of the TP53 codon 72 polymorphism in oral cancer and oral potentially malignant disorders in Argentine patients.

The aim of this work was to evaluate the prevalence of TP53Arg72Pro mutations and their possible relationship with oral carcinoma and oral potentially malignant disorders in Argentine patients. A cross-sectional study was performed on 111 exfoliated cytologies from patients with oral cancer (OC), oral potentially malignant disorders (OPMD) and controls. The TP53Arg72Pro mutations were determined using conventional PCR. We evaluated univariate and multivariate study variables, setting p < 0.05. We found: (a) a low frequency of Pro72 variant in control group and a high frequency in OC and OPMD, as well in OC and oral leukoplakia (OL) diagnosis; (b) multivariate association among the TP53CC genotype and females over 45 years with no tobacco nor alcohol habits with oral lichen planus pathology; (c) multivariate association between the TP53GC genotype and males with alcohol and tobacco habits and OC and OL pathologies. Our results showed that the wild-type Arg72variant was related to control patients and Pro72variant was related to OC and OPMD, in Argentine patients.

Exfoliative cytology as a tool for monitoring pre-malignant and malignant lesions based on combined stains and morphometry techniques.

BACKGROUND: Prevention and early diagnosis have the greatest potential for public health and are the most effective method in the long-term to control oral cancer. The aim was to apply PAP staining together with AgNOR staining and morphometric analysis in oral exfoliative cytology, to determine the sensitivity and specificity of these methods in the detection of malignant changes for the purposes of both initial population monitoring and follow-up. METHODS: AgNOR, Papanicolau, and morphometric tests were conducted in samples of patients with oral cancer, oral potentially malignant disorders and controls (opposite side of lesions). Specificity and sensitivity values for each stain method and the curve under ROC area were estimated. RESULTS: The diagnostic variables which allowed greatest accuracy in identifying malignancy relative to the healthy control were cluster (76.92%), satellite (75.64%), and total (90%). The diagnosis was seen to be associated with PAP and total AgNOR, total AgNOR and PAP, total AgNOR and satellites and clusters, and total AgNOR nuclear area/cytoplasmic area ratio. CONCLUSIONS: The total number of AgNOR is a reliable marker for detecting neoplastic cells; this method increases sensitivity and specificity by decreasing the likelihood of false negatives or positives, as the accuracy obtained was 90%. It is also a low-cost, non-invasive, simple methodology that can be recommended to help the early detection of oral cancer and monitoring of patients with a first diagnosis of cancer.