Vera Aparecida Saddi

Oral squamous cell carcinoma versus oral verrucous carcinoma: an approach to cellular proliferation and negative relation to human papillomavirus (HPV)

Human papillomavirus (HPV) has been cited as a possible initiating agent in the pathogenesis of oral cancer. However, the literature tends to be both controversial and inconclusive about the prevalence of HPV and its potential for proliferation in oral squamous cell carcinoma (SCC). The aim of this study was to investigate the cellular proliferation and the presence of HPV in SCC and verrucous carcinoma (VC). Forty-seven samples of SCC were selected and divided into three groups: 39 SCC, 8 VC, and 9 of normal mucosa (control-CT). Quantitative analyses of all groups showed a greater expression of PCNA, followed by Ki-67 and cyclin B1. A significant difference was observed in cyclin B1 expression in the SCC group compared with VC. PCNA, Ki-67, and cyclin B1 were statistically significant when comparing the SCC and CT groups. However, when SCC and VC were compared, there was no difference in Ki-67 expression. Our results showed that only cyclin B1 had an association with histological grade, and that poorly differentiated tumors presented a higher expression of cyclin B1. Therefore, considerable differences in the cellular proliferation between SCC and VC were observed, and no correlation with HPV was established, since all samples were negative for HPV.

Radiation risk estimation in human populations : Lessons from the radiological accident in Brazil

The development of radiological and nuclear technologies and the deployment of nuclear weapons have made ionizing radiation one of the most studied human mutagens. Exposure to ionizing radiation produces DNA damage which can result in mutation and cancer, making the risk associated with human exposure a critical issue. In this paper we estimate the risk associated with radiation exposure for individuals exposed to 137Cs during the 1987 Goiânia radiological accident. Using combined regression slopes from both the in vivo hprt mutant frequency and micronucleus frequency data we estimated a doubling dose of 173 (+/-47) cGy for these two endpoints. This is in close agreement with the published estimates for low dose rate and chronic exposure to low-LET radiation. We obtained risk estimates of about 24-fold increase in dominant disorders in the post-exposure generation of the directly exposed population. No detectable increase was found in the population at large. The risk of carcinogenesis in the directly exposed population was found to be increased by a factor in the range of 1.4 to 1.5. The small sample size in this study requires a large element of caution with respect to risk estimates interpretation. Moreover, the doubling dose estimates prepared here are derived from lymphocytes. This somatic data may require additional considerations for both cancer and certainly germ-line events. Nevertheless, the risk of carcinogenesis and genetic harm for this population are good indicators of the potential genetic damage imposed by ionizing radiation to the Goiânia population.

Analysis of the BRAF V600E mutation in primary cutaneous melanoma.

BRAF V600E is the most common mutation in cutaneous melanomas, and has been described in 30-72% of such cases. This mutation results in the substitution of valine for glutamic acid at position 600 of the BRAF protein, which consequently becomes constitutively activated. The present study investigated the BRAF V600E mutation frequency and its clinical implications in a group of 77 primary cutaneous melanoma patients treated in a cancer reference center in Brazil. Mutation analysis was accomplished by polymerase chain reaction, restriction fragment length polymorphism, and automated DNA sequencing. The chi-squared and Fischer exact tests were used for comparative analyses. The BRAF V600E mutation was detected in 54/77 (70.1%) melanoma subjects. However, no statistically significant association was found between the presence of the mutation and clinical or prognostic parameters. Our results demonstrated that the BRAF V600E mutation is a common event in melanomas, representing an important molecular target for novel therapeutic approaches in such tumors.

Increased hprt mutant frequencies in Brazilian children accidentally exposed to ionizing radiation

We have examined the effects of ionizing radiation on somatic mutations in vivo, using the hprt clonal assay. The study was performed on blood samples obtained from children exposed during a radiological accident that happened in 1987, in Goiânia, Brazil. The group of children exposed to ionizing radiation includes six males and four females ranging in age from 6 to 14 years at the time of exposure. The radiation doses ranged from 15 to 70 cGy. A Brazilian control group, not exposed to ionizing radiation, was also analyzed under similar conditions. The mean hprt mutant frequency for the exposed group was 4.6 times higher than the control group, although the cloning efficiency from the exposed group was significantly reduced. Linear regression analysis of the mutant frequency and ionizing radiation dose did not show a significant relationship between these two parameters. However, a reliable inverse relationship was demonstrated when the regression analysis was performed with nonselective cloning efficiency and ionizing radiation dose. It was demonstrated that nonselective cloning efficiency diminishes as ionizing radiation dose increases. To correct mutant frequencies for clonal events, the clonal relationship between the hprt mutant clones was examined by T‐cell receptor analysis. The majority of the mutants analyzed represented individual clones, thus validating the observed mutant frequencies.

Human papillomavirus (HPV) genotype distribution in penile carcinoma: Association with clinic pathological factors

Background Penile carcinoma (PC) is a rare, highly mutilating disease, common in developing countries. The evolution of penile cancer includes at least two independent carcinogenic pathways, related or unrelated to HPV infection. Objectives To estimate the prevalence, identify HPV genotypes, and correlate with clinicopathological data on penile cancer. Methods A retrospective cohort study involving 183 patients with PC undergoing treatment in a referral hospital in Goiânia, Goiás, in Midwestern Brazil, from 2003 to 2015. Samples containing paraffin embedded tumor fragments were subjected to detection and genotyping by INNO-LiPA HPV. The clinicopathological variables were subjected to analysis with respect to HPV positivity and used prevalence ratio (PR), adjusted prevalence ratio (PRa) and 95% confidence interval (CI) as statistical measures. Results The prevalence of HPV DNA in PC was 30.6% (95% CI: 24.4 to 37.6), high-risk HPV 24.9% (95% CI: 18.9 to 31.3), and 62.5% were HPV 16. There was a statistical association between the endpoints HPV infection and HPV high risk, and the variable tumor grade II-III (p = 0.025) (p = 0.040), respectively. There was no statistical difference in disease specific survival at 10 years between the HPV positive and negative patients (p = 0.143), and high and low risk HPV (p = 0.325). Conclusions The prevalence of HPV infection was 30.6%, and 80.3% of the genotypes were identified as preventable by anti-HPV quadrivalent or nonavalent vaccine. HPV infections and high-risk HPV were not associated with penile carcinoma prognosis in this study.

Padrão de metástase no câncer de mama triplo negativo

Introduction: Triple negative breast cancers (TNBC) are clinically heterogeneous malignancies that do not present receptors of the estrogen, progesterone and HER2 (ERBB2 or NEU). TNBC are among the most aggressive and deadly breast cancer subtypes. Objective: The present study aimed to elucidate the metastatic pattern of TNBC and attempt to correlate it to age, histology, tumor grade, tumor size, and other clinicopathological variables. Methods: 140 clinical files of patients with breast cancer in Araújo Jorge Hospital in Goiânia (GO), during the period 1998-2010, were selected; among these, 75 cases (53.6%) with TNBC diagnosis were found. Results: The significant variables were tumor size (p=0.0497) and number of metastatic lymph nodes (p=0.002). During the period of five years of observation, metastatic disease occurred in over half of all patients (52.0%). The most common sites of recurrence were lung, bone, and brain. Conclusion: Our finds concluded that patients with TNBC feature a more aggressive type of tumor, requiring increased vigilance in the early years of follow-up. Trabalho realizado na Pontifícia Universidade Católica de Goiás (PUC-Goiás) – Goiânia (GO), Brasil. Departamento de Medicina da PUC-Goiás – Goiânia (GO), Brasil. Faculdade de Enfermagem da Universidade Federal de Goiás (UFG) – Goiânia (GO), Brasil. Programa de Pós-graduação em Ciências da Saúde da UFG – Goiânia (GO), Brasil. Laboratório de Oncogenética e Radiobiologia (DON), Laboratório de Transplante de Medula Óssea (TMO), Hospital Araújo Jorge (HAJ), Associação de Combate ao Câncer em Goiás (ACCG) – Goiânia (GO), Brasil. Programa de Pós-graduação em Ciências Ambientais e Saúde (MCAS) da PUC-Goiás – Goiânia (GO), Brasil. Endereço para correspondência: Antonio Márcio Teodoro Cordeiro Silva – Rua 227A, 72, apto. 301 – Setor Universitário – CEP: 74610-155 – Goiânia (GO), Brasil – E-mail: marciocmed@gmail.com Conflito de interesses: nada a declarar. Recebido em: 08/03/2016. Aceito em: 17/08/2016 DOI: 10.5327/Z201700010003RBM