Immunohistochemical study of the neural development transcription factors (TTF1, ASCL1 and BRN2) in neuroendocrine prostate tumours. / Estudio inmunohistoquímico de los factores de trancripción de desarrollo neural (TTF1, ASCL1 y BRN2) en los tumores neuroendocrinos de próstata.

OBJECTIVE: Prostatic small-cell neuroendocrine carcinoma is an uncommon malignancy that constitutes 0.5-1% of all prostate malignancies. The median cancer-specific survival of patients with prostatic small-cell neuroendocrine carcinoma is 19 months, and 60.5% of the patients have metastatic disease. Neural development transcription factors are molecules involved in the organogenesis of the central nervous system and of neuroendocrine precursors of various tissues, including the suprarenal gland, thyroid glands, lungs and prostate. MATERIAL AND METHODS: We present 3 cases of this uncommon condition, applying the new World Health Organisation criteria. We conducted studies through haematoxylin and eosin staining and analysed the expression of the neural development transcription factors achaete-scute homolog like 1, thyroid transcription factor 1 and the class III/IV POU transcription factors, as a new research line in the carcinogenesis of prostatic neuroendocrine tumours. RESULTS: In case 1, there was no TTF1 immunoexpression. Cases 2 and 3 had positive immunostaining for ASCL1, and Case 1 had negative immunostaining. BRN2 immunostaining was negative in case 1 and positive in cases 2 and 3. CONCLUSION: The World Health Organisation does not recognise any molecular or genetic marker with prognostic value. ASCL-1 is related to the NOTCH and WNT signalling pathways. ASCL-1, TTF1 and BRN2 could be used for early diagnosis and as prognostic factors and therapeutic targets.

Microcytic carcinoma of the urinary bladder: Experience over 22 years.

INTRODUCTION: Microcytic carcinoma of the urinary bladder or bladder Small Cell Carcinoma (SCC) is a rare entity, characterised by an aggressive behaviour, with a poor prognosis, elevated metastatic potential, and is commonly found in older patients and in advanced disease stages. Here we present our experiences with the behaviour of the disease and the treatments applied. MATERIAL AND METHOD: This was a retrospective study on patients diagnosed with bladder SCC in our hospital between February 1992 and February 2014. We analysed the demographic and clinical characteristics of the tumour, the applied treatments and survival. We performed a descriptive statistical analysis of the median follow-up time, Overall Survival (OS) and Cancer-Specific Survival (CSS), using the SPSS statistical package v. 15.0. RESULTS: Over 22 years, 20 patients with an average age of 75 years were diagnosed with bladder SCC (2 female). The predominant symptom was macroscopic haematuria (75%). After the first transurethral resection (TUR) of the bladder and the histological diagnosis, 35% (7 patients) did not receive additional treatment, 15% (3 patients) were treated with chemoradiotherapy (CRT), 10% (2 patients) with TUR, 15% (3 patients) with chemotherapy (QT), 5% (1 patient) with TUR associated to CRT, 5% (1 patient) with radical surgery, 5% (1 patient) with radical surgery treatment followed by adjuvant CRT, 5% (1 patient) with palliative surgery (hypogastric arteriae ligation) followed by adjuvant QT and 5% (1 patient) with hemostatic radiotherapy (RT). With a median follow-up time of 13.8 months, the OS was 14.48 months (95% CI: 6.22 - 22.75) and the CSS 18.04 months (95% CI: 6.51-29.57). Only 10% (2 patients) survived till the end of the study. CONCLUSION: Microcytic carcinoma of the urinary bladder is a rare and aggressive entity commonly diagnosed in males of advanced age and in advanced disease stages. It has a poor prognosis and reduced survival. Due to its aggressiveness previous to the initial diagnosis, a cystectomy is only possible in very few cases; therefore multimodal treatment is necessary. This treatment is yet to be defined.