Original ArticlesLoss of p16INK4A Expression Is Associated With Allelic Imbalance/Loss of Heterozygosity of Chromosome 9p21 in Microdissected Malignant Peripheral Nerve Sheath TumorsSabah, Muna MRCPath; Cummins, Robert BSc; Leader, Mary FRCPath; Kay, Elaine FRCPath Author Information Department of Histopathology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland Reprints: Dr. Muna Sabah, Department of Histopathology, Education and Research Centre, The Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland (e-mail: [email protected]) Received for publication November 24, 2003; accepted July 15, 2004 Applied Immunohistochemistry & Molecular Morphology: March 2006 - Volume 14 - Issue 1 - p 97-102 doi: 10.1097/01.pai.0000143787.80564.f5 Buy Metrics Abstract The p16INK4A is a tumor suppressor gene on the short arm of chromosome 9p21. The product of the p16INK4A acts as a negative cell cycle regulator by inhibiting G1 cyclin-dependent kinases that phosphorylate the retinoblastoma protein. This study was designed to assess the frequency of genetic loss of 9p21 and to determine the role of p16INK4A the pathogenesis of sporadic and neurofibromatosis 1 (NF1)-associatisd malignant peripheral nerve sheath tumors (MPNSTs). The authors examined 15 cases for p16 protein expression and 10 cases for allelic imbalance (AI)/loss of heterozygosity (LOH) of chromosome 9p. DNA was microdissected from normal and neoplastic tissues. AI/LOH analysis was performed using six microsatellite markers on the 9p region. On immunohistochemical analysis 80% of cases showed abnormal expression of p16. Similarly, 8 of 10 cases revealed genetic loss with at least one microsatellite marker. The most frequent deletion was that within the coding sequence. Of p16INK4A at me D9S974 locus. These findings emphasize the role of loss of p16INK4A in the development of both sporadic and NF1-associated MPNSTs. © 2006 Lippincott Williams & Wilkins, Inc.