Association of human papillomavirus (HPV), p16, p53 and p63 expression with non-bilharzia-associated squamous cell carcinoma of the bladder and algorithm construction for histopathological grading prediction

ABSTRACT Objective To investigate the expression of human papillomavirus (HPV), p16, p53, and p63 in non-schistosomiasis-related squamous cell carcinoma of the bladder and to develop an accurate and automated tool to predict histological classification based on clinicopathological features. Methods Twenty-eight patients with primary bladder pure squamous cell carcinoma who underwent cystectomy or transurethral resection of bladder tumor (TURBT) for bladder cancer between January 2011 and July 2017 were evaluated. Clinical data and follow-up information were obtained from medical records. Formalin-fixed, paraffin-embedded surgical specimens were used for immunohistochemical staining for p16, p53, and p63. Human papillomavirus detection was evaluated by PCR. Statistical analysis was performed, and statistical significance was set at p<0.05. Finally, decision trees were built to classify patients' prognostic features. Leave-one-out cross-validation was used to test the generalizability of the model. Results Neither direct HPV detection nor its indirect marker (p16 protein) was identified in most cases. The absence of p16 was correlated with less aggressive histological grading (p=0.040). The positive p16 staining detection found only in pT1 and pT2 cases in our sample suggests a possible role for this tumor suppressor protein in the initial stages of bladder squamous cell carcinoma. The decision trees constructed described the relationship between clinical features, such as hematuria/dysuria, the level of tumor invasion, HPV status, lymphovascular invasion, gender, age, compromised lymph nodes, and tumor degree differentiation, with high classification accuracy. Conclusion The algorithm classifier approach established decision pathways for semi-automatic tumor histological classification, laying the foundation for tailored semi-automated decision support systems for pathologists.

Efeito da laserterapia sobre modelo experimental de inflamação granulomatosa / Effect of the laser therapy on experimental model of granulomatous inflammation

Na inflamação antigênica induzida por corpo estranho, observa-se a formação de células gigantes, sendo que os mecanismos envolvidos neste processo não se encontram completamente compreendidos. Na literatura, alguns trabalhos apontam para o efeito terapêutico do laser na resposta inflamatória e na cicatrização de feridas, mas, esta ação também não foi explicada de forma completa. A ação do laser As-Ga na inflamação induzida pela introdução de lamínulas de vidro no dorso de camundongos foi avaliada. Para os dois grupos tratados e não-tratados, utilizou-se trinta e seis camundongos adultos e a laserterapia foi aplicada 24h, 48h, 72h, 5, 7, 14 e 21 dias, após a indução da inflamação. O sacrifício ocorreu 7, 14 e 21 dias após cirurgia. O grupo tratado apresentou grau mais avançado no fechamento da cirurgia em relação ao grupo não-tratado. O número de células gigantes nos animais tratados com laser foi significativamente maior, assim como os valores do material fibroso, principalmente no 14 e 21 dias. Na indução experimental de inflamação granulomatosa em camundongos, a laserterapia tem ação inflamatória nas primeiras semanas e a partir dos vinte e um dias a resposta caracteriza-se como antiinflamatória.

In the antigenic induced inflammation by foreign body, the giant cells formation is observed, and the mechanisms involved in this process are not totally understood. In literature, we find some works that therapeutic effect of laser showed good inflammatory answer and wound healing, but this action was also not well explained. The effect of the laser As-Ga in the induced inflammation was evaluated by inserting the glass coverslip on the back of the mice. For the two treated groups and non-treated, it was used thirty six male adult mice and the laser therapy was applied 24:00, 48:00, 72:00h and 5, 7, 14 and 21 days, after inflammation induction. The sacrifice was performed 7, 14 and 21 days after surgery. The treated group presented more advanced stage of closing the surgery in relation to the non-treated group. The number of giant cells in the treated mice with laser was significantly higher, as well as values of the fibrous material, in the 14 and 21 days. On experimental induction of granulomatous inflammation in mice, the laser therapy has inflammatory action in the first weeks and after twenty-one days has anti-inflammatory action.