Approximately 80% of bladder tumors are urothelial superficial papillary carcinomas (USPC). Despite a generally good prognosis, these tumors have a strong propensity to recur and about 1/3 of them compared to disease progression. Histological assessment of these superficial tumors is not sufficiently discriminator in predicting prognosis; therefore, we decided to evaluate the prognostic significance of p53 and Ki‐67 immunoexpression in low‐grade (GI‐II) USPC in order to predict the potential outcome of these tumors. P53 and Ki‐67 immunoexpression were studied in function of recurrence‐free and progression‐free survival in 159 primary superficial bladder tumors. A prognostic risk model based on grade, stage and multifocality was also evaluated. P53 accumulation was significantly related to tumor progression (p=0.006). High Ki‐67 index (≥18%) and multifocality were significantly related to recurrence (both p=0.0001) and progression‐free survival (both p=0.0001) and were independent prognostic factors in the multivariate analysis. The prognostic risk model based on grade, stage and multifocality was not an efficient discriminator of outcome. Adding the Ki‐67 index into the risk model, single pTa/T1‐GI Ki‐67 positive tumors, usually classified as low risk, were reclassified as of intermediate risk. After this reclassification, the risk group model identified a subgroup of pTa/T1‐G1 with a high risk of recurrence and progression. Ki‐67 index is a reliable prognostic marker in urothelial superficial bladder carcinoma and, when included into a risk profile classification of the low‐grade USPC, the accuracy of the prognostic discrimination is enhanced.

High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T). In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn. From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344–5.254); P=0.005), maintenance schedule (HR=0.480; (0.246–0.936); P=0.031) and multifocallity (HR=2.065; (1.033–4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148–0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death. s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy.

Background: Of patients with superficial bladder cancer, a group are still at risk of disease recurrence, progression and death from their cancer after curative treatment. Angiogenesis is a crucial pathogenic mechanism for this type of urothelial cell carcinoma (UCC), and is a potential therapeutic target. However, the selection of the appropriate patients remains a dilemma. Patients and methods: Vascular endothelial growth factor (VEGF) expression and the presence of angiogenesis and occurrence of CD31, CD34, endoglin and factor VIII immunoexpression, were evaluated in 66 superficial papillary UCCs of the bladder and were correlated with classical histopathological factors and disease outcome. Results: VEGF immunoreactivity was observed in 100% of cases, and more intensely in the luminal surface. The presence of microvessel clusters independently of a fibrovascular core was observed in 22.7% of cases. Of these, the T1/G2 subgroup had an independent and significantly lower recurrence-free survival (P = 0.0002). Conclusions: These results indicate that the presence of angiogenesis in tumour urothelium is a potential prognostic factor in superficial UCC, particularly in T1/G2 tumours, and may be used to select patients for anti-angiogenic treatments.

Background: Multiple sclerosis is an autoimmune disease of the central nervous system with neurological and motor symptoms that affect the orofacial region. The aim of this work is to present a patient that lacks the three classic orofacial manifestations but has other less common clinical alterations. Case presentation: A 49-year-old female patient diagnosed with long-term relapsing–remitting multiple sclerosis visited the dentist complaining of mild but persistent orofacial pain including the temporomandibular joint and pain not specific to any tooth. She presented mucosal irritation, xerostomia, halitosis, and localized gingivitis. There was excessive wear of the upper and lower incisal edges and the occlusal faces of the upper canines and loss of six teeth due to caries. After a clinical oral examination, the diagnosis was temporomandibular joint disorder, gingivitis, dental hypersensitivity, bruxism, hyposalivation, xerostomia, and halitosis. Conclusions: Patients with multiple sclerosis present classic orofacial manifestations. Although these were not observed in this patient, she had others, such as gingivitis, tooth hypersensitivity, and bruxism. In addition, despite few studies associating a higher prevalence of caries with these patients, the number of carious and missing teeth in this patient highlight the evidence that multiple sclerosis has had a significant impact on the patient’s dental status over the years.