Loss of expression of the Neural Cell Adhesion Molecule 1 (NCAM1) in atypical teratoid/rhabdoid tumors: a new diagnostic marker?

Background: Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive embryonal tumors of the central nervous system. They are largely characterized by inactivating mutations of the SMARCB1 tumor suppressor gene. AT/RT patients have a very poor prognosis and no standard therapeutic protocol has been defined yet. Recently, multimodal therapy with multiple drug combinations has slightly improved the overall survival, however drug toxicity remains high. In this scenario, a better understanding of the pathophysiology of the disease is needed. Methods: We evaluated the gene expression profile of AT/RT samples to find new genetic factors contributing to the pathophysiology of the disease. We found target genes significantly differentially expressed between AT/RT and medulloblastoma (MB), the most common embryonal brain tumor. The mRNA expression was validated by quantitative real-time PCR and, at the protein level, expression was validated by immunohistochemistry in an independent set of tumors. Results: The Neural cell adhesion molecule 1 (NCAM1) gene was found to be consistently downregulated in AT/RT samples when compared to MB and normal brain tissue. Immunohistochemistry showed that the expression of NCAM1 in AT/RT was significantly lower than that of MB. Conclusion: NCAM1 is an important molecule involved in neuron-to-neuron and neuron-to-muscle adhesion during development. Downregulation of NCAM1 has been implicated in several human cancers suggesting that it might have a tumor repressor role. In this study we found a significantly reduced expression of NCAM1 in AT/RT when compared to MB and we suggest that this feature can be used as a diagnostic marker, along with demonstration of SMARCB1 (INI1) or SMARCA4 (BRG1) inactivation. The roles of NCAM1 in the pathophysiology of AT/RT are still to be determined (AU)

Atypical Teratoid Rhabdoid Tumors in Adult Patient with Multiple Lesions

Primary atypical teratoid/rhabdoid tumor(AT/RT) of the central nervous system is a recently described, highly malignant neoplasm that usually occur in the posterior fossa of children. Although AT/RT usually occurs in young children, AT/RT is being recognized in adults with increasing frequency. The authors report 49-year-old man with multiple AT/RT lesions (right lateral ventricle, right temporal lobe and right cerebellum). Histopathologic findings showed typical rhabdoid cells with eccentric nuclei and prominent nucleoli. Eventhough the tumor was removed, a patient was dead in one month after surgery due to recurrence and rapid regrowth of the tumor.

Intracranial Atypical Teratoid/Rhabdoid Tumor: Retrospective Analysis in a Single Institution / 대한소아혈액종양학회지

PURPOSE: Intracranial atypical teratoid/rhabdoid tumor (ATRT) is an extremely rare and aggressive tumor of early childhood. In this study, we evaluated the clinical characteristics, therapeutic approaches and outcomes of children who were treated at Seoul National University Children's Hospital (SNUCH). METHODS: We reviewed the clinical records of seven patients who were diagnosed as ATRT at SNUCH between January 2000 and July 2005. RESULTS: Of the seven patients, three patients were male and four were female. Median age at diagnosis was 13 months ranging from 3 months to 67 months. The tumors occurred in the infratentorial area in six and at multiple sites in one patient. Metastatic disease at diagnosis was present in two patients. One showed cerebrospinal fluid (CSF) dissemination and the other showed bony metastasis. Tumor excision was performed in all patients, and with the exception of two cases that refused further treatment, five patients received postoperative chemotherpay. One patient with CSF dissemination received radiotherapy and intrathecal chemotherapy as well. Of all the patients who received chemotherapy, two patients died during treatment because of tumor progression. The chemotherapy regimen was changed in three patients during treatment because the tumor showed poor response to chemotherapy. The median length of follow-up for five patients receiving chemotherapy was 6 months and the overall survival (OS) and event free survival (EFS) were 33.3% and 0%, respectively. CONCLUSION: Though various therapeutic approaches have led to improved survival in ATRT, the prognosis of ATRT is dismal compared with other brain tumors. A precise pathologic diagnosis is crucial and intensified treatment modalities should be considered according to the extent of tumor. To establish optimal treatment guidelines, a cooperative prospective study is needed and the efficacy of individual regimens should be analyzed.