Development and characteristics of preclinical experimental models for the research of rare neuroendocrine bladder cancer.

PURPOSE: For rare cancers such as neuroendocrine bladder cancer treatment options are limited due partly to the lack of preclinical models. Techniques to amplify rare primary neuroendocrine bladder cancer cells could provide novel tools for the discovery of drug and diagnostic targets. We developed preclinical experimental models for neuroendocrine bladder cancer. MATERIALS AND METHODS: Fresh tumor tissue from 2 patients with neuroendocrine bladder cancer was used to establish in vitro and in vivo models. We analyzed additional archived tissues in the National Center of Tumor Diseases tissue bank from patients with neuroendocrine bladder cancer. Primary tumor samples were collected during radical cystectomy. PHA-665752 was used to inhibit MET in animal models and cell cultures. The expression of markers and drug targets in neuroendocrine bladder cancer was determined by flow cytometry. The growth of neuroendocrine bladder cancer in vitro was determined by counting live cells. Tumor growth in mice was assessed by measuring tumor volume. Groups were compared using the nonparametric Kruskal-Wallis test. RESULTS: Xenograft models and serum-free cultures of neuroendocrine bladder cancer cells allowed screening for cell surface markers and drug targets. We found expression of the HGF receptor MET in neuroendocrine bladder cancer cultures, xenograft models and primary patient sections. The growth of neuroendocrine bladder cancer spheroids in vitro depended critically on HGF. Treatment of neuroendocrine bladder cancer bearing mice with a MET inhibitor significantly decreased tumor growth compared to that in control treated mice. CONCLUSIONS: Neuroendocrine bladder cancer xenografts and serum-free cultures provided suitable models in which to identify diagnostic markers and therapeutic targets. Using the models, we noted HGF dependent growth of human neuroendocrine bladder cancer and identified MET as a new treatment target for neuroendocrine bladder cancer.

Primary neuroendocrine breast cancer-an unusual occurrence.

Primary breast neuroendocrine neoplasms (BNENs) are a rare form of breast cancer, accounting for less than 0.1% of all breast malignancies. These neoplasms have a similar clinical presentation as conventional breast carcinomas, differing mainly in their histopathology and expression of neuroendocrine (NE) markers, chromogranin and synaptophysin. Owing to their rarity, current knowledge of these tumours comes mainly from corroborative case reports or retrospective case series. There is hence a lack of randomised data on the treatment of these entities and current protocol suggests similar treatment as that of conventional breast carcinomas. We report the case of a 48-year-old with a breast mass, which on further work-up was diagnosed as locally advanced carcinoma breast, that required a mastectomy and axillary node dissection on the same side and revealed NE differentiation on histopathological examination. Hence, immunohistochemical staining was indicated which confirmed NE differentiation. We discuss the current knowledge on incidence, demographics, diagnosis, histopathological and staining characteristics, prognostic factors and treatment modalities of BNENs.

Neuroendocrine Cancer of the Breast: A Rare Entity.

Neuroendocrine breast cancer (NEBC) is a rare histotype of breast carcinoma that presents, in most cases, positive hormone receptors and negative HER2. Indeed, the analysis of gene expression profiles revealed that NEBC belongs mainly to the luminal subtype. Cases of HER2-positive and triple-negative NEBC are rare. The cardinal treatment of early NEBC is surgery, similar to the treatment of invasive non-special histological type carcinoma. The use of radiotherapy follows the criteria applied in infiltrating breast cancer of non-special histotype. In the post-operative phase, therefore after the surgical treatment of mammary quadrantectomy, or mastectomy associated with homolateral sentinel lymph node removal ± axillary dissection, based on the histopathological characteristics of the tumor, the use of chemotherapy (anthracycline + taxane) and/or hormone therapy, whether or not associated with anti-HER2 therapy (trastuzumab) is the rule. Literature data report the use of cisplatin and etoposide, as in small cell lung cancers. Most of the information currently available derive from single case reports or a series of clinical cases; it follows the difficulty of formulating definite recommendations on the correct management of this histological type of breast cancer. This review describes available knowledge on this rare entity to improve the diagnostic and therapeutic strategies and offer insights to stimulate exploration of the many aspects still unknown.