No evidence for epidermal growth factor receptor amplification and overexpression in atypical teratoid/rhabdoid tumors

Excerpt

Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant embryonal neoplasm of the central nervous system most often affecting young children [9]. As in malignant rhabdoid tumors of the kidney, rhabdoid cells displaying intracytoplasmic inclusions and prominent nucleoli are the key histological features [8] and inactivating mutations of the SMARCB1 gene (hSNF5/INI-1) located on chromosome 22q11.2 represent a crucial step in tumor progression [1, 4]. Unfortunately, the rapidly increasing knowledge has not yet been translated into successful treatment approaches and the prognosis of ATRT remains dismal [9]. Epidermal growth factor receptor (EGFR) overexpression resulting from amplification and/or increased transcription has been described for several malignant pediatric tumors such as neuroblastoma, osteosarcoma and pediatric glioblastoma [2]. The reported EGFR expression in malignant rhabdoid tumors of the kidney [6] along with the observation that blockade of EGFR signaling by the tyrosin kinase inhibitors such as gefitinib affected growth of rhabdoid cell lines both in vitro [6, 7] and in vivo [6] has fueled hope that blockade of EGFR signaling might complement therapy regimens of ATRT as recently reported for other malignant solid tumors refractory to treatment in children [3]. In contrast to other pediatric brain tumors [2], however, EGFR expression has not been examined in ATRT. We therefore investigated EGFR amplification and protein expression in a series of ATRT in order to provide a rationale for future therapeutic trials. …