title: Apolipoprotein D is down-regulated during malignant transformation of neurofibromas.
abstract: Apolipoprotein D (apoD) expression was studied in nonneoplastic peripheral nerve, neurofibromas (NFs), and malignant peripheral nerve sheath tumors (MPNSTs) by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. Multiplex quantitative polymerase chain reaction for messenger RNA was performed on a series of formalin-fixed and paraffin-embedded specimens that included 9 MPNSTs, 12 NFs, and 4 normal peripheral nerves. The average apoD expression was 108-fold decreased (DeltaCt = -7.3) in the MPNSTs compared with the NFs (P < .05). ApoD expression levels were 3.0-fold elevated (DeltaCt = 1.7) in the NFs compared with nonneoplastic peripheral nerve (P < .05). In situ hybridization for apoD RNA was performed on a separate series of 10 cases in which each microscopic section included both MPNST and the NF from which it arose. These studies confirmed elevated apoD expression in NFs compared with MPNSTs and demonstrated that this expression was variable among individual cells within the NFs. Differential expression by immunohistochemistry could only be demonstrated in selected areas, most likely because apoD protein is a small molecule that is secreted out of the cell into the extracellular space and plasma. ApoD expression initially increases a small amount with the formation of NFs from nonneoplastic peripheral nerve and subsequently decreases markedly as NFs transform into MPNSTs. This expression pattern may serve as a marker for cell cycle inhibition during peripheral nerve tumorigenesis.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. stephen_hunter@emory.org
authors.forename: Stephen
authors.initials: S
authors.lastname: Hunter
authors.forename: Sharon
authors.initials: S
authors.lastname: Weiss
authors.forename: Chen-Yih
authors.initials: CY
authors.lastname: Ou
authors.forename: David
authors.initials: D
authors.lastname: Jaye
authors.forename: Andrew
authors.initials: A
authors.lastname: Young
authors.forename: Josiah
authors.initials: J
authors.lastname: Wilcox
authors.forename: Jack L
authors.initials: JL
authors.lastname: Arbiser
authors.forename: David
authors.initials: D
authors.lastname: Monson
authors.forename: John
authors.initials: J
authors.lastname: Goldblum
authors.forename: John D
authors.initials: JD
authors.lastname: Nolen
authors.forename: Vijay
authors.initials: V
authors.lastname: Varma
mesh_terms: D001053:Apolipoproteins / Q000378:metabolism*; D053399:Apolipoproteins D; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018317:Nerve Sheath Neoplasms / Q000378:metabolism / Q000473:pathology; D009455:Neurofibroma / Q000378:metabolism* / Q000473:pathology*; D010524:Peripheral Nervous System Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016133:Polymerase Chain Reaction
chemical_list: D001053:Apolipoproteins; D053399:Apolipoproteins D