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Int J Clin Exp Pathol 2010;3(5):515-521

Original Article
CD44 and p53 immunoexpression patterns in NF1 neoplasms- indicators of malignancy
and infiltration

Nicole D. Riddle, Lemuel Gorden, Mumtaz V.Rojiani, Ardeshir Hakam, Amyn M. Rojiani

Department of Pathology and Cell Biology, University of South Florida, Tampa, FL, USA; Department of Pathology, University of Florida,
Gainesville, FL, USA; Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL, USA

Received April 21, 2010, accepted May 20, 2010, available online June 12, 2010

Abstract: Neurofibromatosis type 1 (NF1) provides a unique system to evaluate the complete range of neoplastic expressions, from
encapsulated benignity to invasiveness and malignancy. This study was aimed at determining whether CD44 and p53 may serve as indicators
of malignant progression of neurofibroma. CD44, a transmembrane glycoprotein receptor for hyaluronic acid, and participates in cell-
extracellular matrix interactions and migration. CD44 may play a vital role, either through under or overexpression, with invasion and
metastases of tumors, altering their ability to infiltrate the adjacent tissue.  The tumor suppressor gene, p53, has also been implicated in
malignant progression of various human tumors including malignant peripheral nerve sheath tumors (MPNST).  A total of 44 tumors from 33
patients with NF1 were evaluated with an anti-human CD44H, CD44 splice variant v6 and anti-p53 monoclonal antibodies. Morphologic
expression patterns of expression were evaluated for CD44 while semiquantitative criteria were applied to assess, p53 nuclear positivity.  
Immunoexpression of p53 was markedly higher in 12 of 16 MPNST (75%).  Thirteen of 28 (46%) benign neurofibroma also had some
expression of p53 above ‘normal level’, although much lower than the MPNST.  Plexiform neurofibroma did not differ from other benign lesions
in their expression of p53. Our results suggest that p53 mutation as evidenced by immunohistochemical overexpression is a factor in
malignant transformation and progression of neurofibroma. 70% of benign neurofibroma demonstrated some, usually focal, CD44 positivity.
The pattern of CD44 expression in plexiform neurofibroma was revealing, as it was maximal in the ‘nonencapsulated’ portions of the tumors.  
Eight of 11 (72%) locally infiltrative cutaneous neurofibroma and 13 of 16 (81%) MPNST exhibited diffuse CD44 positivity. CD44v6 expression
was positive in control tissues but was not identified in any of tumor samples. Also, within the confines of encapsulated tumors CD44
expression is limited, while in poorly circumscribed neurofibroma CD44 expression is upregulated. This is interpreted as a reflection of the
interaction of CD44+ tumor cells with extracellular matrix, hence facilitating infiltrative behavior. IJCEP1004006).

Key words: Neurofibromatosis type 1 (NF1), CD44, p53, tumor markers, infiltration, immunohistochemistry

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Address all correspondence to:
Amyn M Rojiani M.D., Ph.D.
Professor of Pathology
Department of Pathology and Cell Biology
12901 Bruce B Downs Blvd. MDC 11
Tampa, FL 33610
Phone: (813) 974-8750
Fax: (813) 974-5536
Email: arojiani@health.usf.edu