CD44 and p53 immunoexpression patterns in NF1 neoplasms – indicators of malignancy and infiltration

Department of Pathology and Cell Biology, University of South Florida, Tampa, FL 33610, USA.
International journal of clinical and experimental pathology (Impact Factor: 1.89). 01/2010; 3(5):515-21.
Source: PubMed


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.

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Available from: Nicole D Riddle, Dec 03, 2015
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    • "The clinical significance of isolated neurofibromas has not been well studied. The natural history of these lesions is typically benign, but malignant transformation has been reported, particularly in association with NF1 and in larger, plexiform lesions [14]. With such low incidence and very few cases reported, long-term follow-up goals and screening are still undetermined at this time, but close clinical follow-up of these patients is important to exclude neurofibromatosis and its associated risk of malignant transformation. "
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    ABSTRACT: Neurofibromatosis is a genetic disorder manifested by characteristic cutaneous lesions called neurofibromas. There are two distinct neurocutaneous syndromes named neurofibromatosis type 1 (also called von Recklinghausen disease or NF1) and neurofibromatosis type 2 (NF2). NF1 is by far the most common presentation and is caused by an autosomal dominant mutation in the NF1 gene mapped to chromosome 17q11.2. The literature shows that gastrointestinal involvement is noted in systemic neurofibromatosis in up to 25% of patients, but isolated intestinal neurofibromatosis is a very rare manifestation. We herein present the case of a 70-year-old woman who was diagnosed with an isolated colonic neurofibroma without any systemic signs of neurofibromatosis; only a few case reports of this condition have been published to date.
    Full-text · Article · Sep 2013 · Case Reports in Gastroenterology
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    • "No consensus has yet been reached in the medical community as to whether such lesions represent different phenotypic manifestations of neurofibromatosis or separate and distinct entities entirely [14]. Though typically benign lesions, they have been reported to undergo malignant transformation, particularly when associated with NF1 and in larger, plexiform lesions [15]. Though uncommon, there are reports in the literature of neurofibromas and nerve sheath tumors presenting as lymphomas [16, 17]. "
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    ABSTRACT: Solitary neurofibromal colonic polyps are a rare entity, particularly outside the setting of neurofibromatosis type 1. The clinical significance of such lesions has not yet been established. Though typically benign tumors, neurofibromas have been reported to undergo malignant transformation, with an increased risk of malignancy when associated with neurofibromatosis. In this case report, we present the rare case of a man found to have an isolated colonic neurofibroma without any personal/family history or clinical features of neurofibromatosis. A 59-year-old man with a history of dyslipidemia and degenerative joint disease presented for a routine screening colonoscopy. The colonoscopy revealed no abnormalities except a 3 mm transverse colon polyp and another 4 mm polyp in the descending colon. Biopsy results showed the descending colonic polyp to be a tubular adenoma; however, multiple levels of the 3 mm transverse colon polyp revealed interlacing bundles of spindle cells extending into the lamina propria with comma-shaped nuclei consistent with findings seen in neurofibroma. Isolated colonic neurofibromas are rare and understudied. While they are usually benign, they may undergo malignant transformation, especially when associated with neurofibromatosis. Thus, patients presenting with isolated neurofibromas should be followed for development of neurofibromatosis and malignancies.
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    ABSTRACT: Malignant peripheral nerve sheath tumors (MPNSTs) are the most common malignancy associated with NF1. At present, complete surgical removal is the only successful treatment for MPNST, and the outcome for unresectable, recurrent, or metastatic MPNST remains poor. Because 50 % of MPNSTs arise in individuals with NF1, and because the prognosis of NF1-associated MPNST appears to be worse than that of sporadic tumors, many studies of MPNST have used NF1 models and comparisons between sporadic and NF1 MPNST. Currently, molecular analyses and preclinical testing are beginning to aid in the identification of promising therapies to target these neoplasms. Knowledge of the epidemiology, clinical presentation, diagnosis, and prognostic factors for MPNST is anticipated to allow for earlier detection of, and more successful treatment for, MPNST. © 2012 Springer-Verlag Berlin Heidelberg. All rights are reserved.
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