RESUMO
OBJECTIVE: To examine the microRNA (miRNA) expression pattern in tumour samples from patients with progressing and non-progressing upper tract urothelial carcinoma (UTUC) in order to identify putative miRNAs that may be used as prognostic markers. PATIENTS AND METHODS: We conducted a multicentre, retrospective study of formalin-fixed paraffin-embedded tissue samples from 150 patients with UTUC who had undergone radical nephroureterectomy. Global miRNA expression patterns were analysed in 18 selected samples from patients with UTUC using TaqMan arrays. The differential expression of five key miRNAs was validated by quantitative polymerase chain reaction in an independent cohort of 132 samples from patients with UTUC. Models to predict tumour progression and cancer-specific survival that included miRNA expression patterns were developed by Cox regression analysis. RESULTS: Twenty-six miRNAs were found to be aberrantly expressed between samples from patients with progressing and non-progressing UTUC and five of these were selected for subsequent studies. The regression analysis identified tumour stage and miR-31 and miR-149 expression as independently associated with tumour progression and tumour stage and miR-149 expression as independently associated with cancer-specific survival. The risk scores derived from these miRNA models were able to discriminate two groups with a highly significantly different probability of tumour progression (hazard ratio [HR] 4.78; P < 0.001) and death (HR 276; P = 0.004). CONCLUSIONS: There is a differential miRNA expression pattern between patients with progressing and non-progressing UTUC. The identification of new miRNAs associated with a high probability of tumour recurrence and cancer-specific survival in patients with UTUC and their combination in a robust, easy-to-use and reliable algorithm may help tailor treatment and surveillance strategies in these patients.
Assuntos
Carcinoma de Células de Transição/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/biossíntese , RNA Neoplásico/genética , Neoplasias Urológicas/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma de Células de Transição/metabolismo , Humanos , Prognóstico , RNA Neoplásico/biossíntese , Neoplasias Urológicas/metabolismoRESUMO
BACKGROUND: Primary small cell carcinoma of the upper urinary tract (UUT-SCC) is an extremely uncommon disease. The current knowledge of these rare tumors is mainly based on case reports or small series. METHODS: We reported two cases and performed a systematic literature search from 1970 to 2010 for articles on UUT-SCC. Overall, 40 patients with UUT-SCC were reviewed, a database was generated to analyze clinical characteristics, pathological features and therapy outcomes and to attempt in identifying prognostic factors. RESULTS: For the 39 cases with available data, median age was 66.5 years and male-female ratio was 2:1. An Asian ethnic background was more common (59%). Surgery was the standard treatment given to all patients. In 67% of cases, SCC coexisted with another malignant component, including urothelial carcinoma in 62% of patients. Overall median survival was 15 months and the 1-, 2- and 3-year survival rates were 58.4%, 38.1% and 23.8%, respectively. Of all cases, 53.8% developed detectable metastasis in a median delay of 13 months. Pathological stage was the only significant prognostic factor found (p=0.01). Patients who received adjuvant chemotherapy seem to have a higher median survival comparatively to those who did not receive chemotherapy but this was not statistically significant (24 vs. 12 months, p=0.56). CONCLUSIONS: UUT-SCC is an extremely rare tumor characterized by an aggressive clinical course. Local or distant metastases are frequent and survival is poor. Pathological stage appeared to be a prognostic factor for overall survival.
Assuntos
Carcinoma de Células Pequenas/mortalidade , Carcinoma de Células Pequenas/patologia , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Idoso , Biópsia por Agulha , Carcinoma de Células Pequenas/terapia , Quimioterapia Adjuvante , Terapia Combinada , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Doenças Raras , Medição de Risco , Análise de Sobrevida , Neoplasias Ureterais/mortalidade , Neoplasias Ureterais/patologia , Neoplasias Ureterais/terapia , Neoplasias Uretrais/mortalidade , Neoplasias Uretrais/patologia , Neoplasias Uretrais/terapia , Neoplasias Urológicas/terapiaRESUMO
Congenital pulmonary alveolar proteinosis is an uncommon affection, distinct from adult's alveolar proteinosis by its clinical, pathological, etiological and evolutive characteristics. We report two cases of congenital alveolar proteinosis related to a surfactant protein B deficiency. Clinical presentations were similar: the two children were full-term newborns and had swiftly developed respiratory distress. Chest radiography demonstrated bilateral alveolar syndrome. Echocardiography was normal. There was no sign of infection. The two children died respectively at three weeks and two months of life. Lung biopsy showed lesions of alveolar proteinosis in the two cases. Both children were homozygotes for the 121ins2 mutation of the SFTPB gene. Diagnosis of surfactant protein B deficiency must be suspected in congenital alveolar proteinosis. It can be confirmed by the absence of detection of the surfactant B protein by immunohistochemistry on fixed and paraffin-embedded lung tissue or by western blot on bronchoalveolar fluid and by the absence of mRNA by RT-PCR. We report the value of molecular diagnosis for genetic counseling and the possibility of early prenatal diagnosis by trophoblast biopsy.