Atypical teratoid/rhabdoid tumor of the CNS: cytopathology and immunohistochemistry of insulin-like growth factor-II, insulin-like growth factor receptor type 1, cathepsin D, and Ki-67.
Insulin-like growth factor (IGF)-II is a potent growth factor, normally controlled by a number of other factors, including IGF binding proteins and IGF binding protein proteases. In general, the latter increase the bioavailability of IGF by cleaving IGF binding proteins. Cathepsin D (an IGF binding protein protease) was also implicated in tumor invasion. Although IGF-II was implicated in the pathogeneses of various childhood neoplasms, its significance in the pathogenesis of atypical teratoid/rhabdoid tumor of the central nervous system (ATRT-CNS) was not studied to date. We present clinicopathologic features of two cases of ATRT-CNS. In addition, formalin-fixed, paraffin-embedded tissue sections were stained immunohistochemically for IGF-II, IGF receptor type 1, cathepsin D, and Ki-67. Both tumors demonstrated diffuse strong cytoplasmic positivity for IGF-II, diffuse cytoplasmic and focal membranous positivity for IGF receptor type I, and diffuse cytoplasmic positivity for cathepsin D. The Ki-67 labeling indices were 10.0% and 1.4%. We conclude that ATRT-CNS cells express both IGF-II and IGF receptor type 1, supporting the hypothesis that autocrine/paracrine stimulation of cell growth by IGF-II might be one mechanism involved in ATRT-CNS tumorigenesis. Cathepsin D expressed by the tumor cells might also be involved in both tumor cell invasion and growth. The exact pathogenesis of ATRT-CNS remains to be elucidated.
Ogino
S
S
Institute of Pathology, Case Western Reserve University and University Hospitals of Cleveland, Ohio 44106, USA.
Cohen
M L
ML
Abdul-Karim
F W
FW
D000293:Adolescent; D002402:Cathepsin D / Q000032:analysis; D016543:Central Nervous System Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D017526:Receptor, IGF Type 1 / Q000032:analysis; D018335:Rhabdoid Tumor / Q000378:metabolism / Q000473:pathology*; D013724:Teratoma / Q000378:metabolism / Q000473:pathology*
D019394:Ki-67 Antigen; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D002402:Cathepsin D