Ki-67 proliferation-index (MIB-1) of neurofibromas in neurofibromatosis type 1 patients. 2003

R E Friedrich, and C Hagel, and Z Brehme, and L Kluwe, and V F Mautner
Department of Oral and Maxillofacial Surgery, Eppendorf University Hospital, University of Hamburg, Martinistr. 52, D-20246 Hamburg, Germany. rfriedriguke.uni-hamburg.de

OBJECTIVE The aim of this study was to analyse the proliferation rate of neurofibromas, in neurofibromatosis type 1 (NF1) patients in order to find out whether tumor growth can be correlated with the different subtypes, size and localisation of tumors, or gender. Large tumors and those localisations that do not allow a complete resection, e.g. the trigeminal branch plexiform neurofibromas, often require repeated surgical interventions. Therefore, the question whether partial resection is associated with alterations of the tumor type and proliferation is of great interest. METHODS We investigated 317 specimens of 96 patients. Twenty-five specimens were identified as local recurrences, all of them being consecutive resections in the previously operated area. All patients were NF 1-affected individuals who fulfilled the US National Institute of Health consensus criteria for defining the disease. The proliferation index (PI) was assessed on formalin-fixed, paraffin-embedded tissue stained with the MIB- 1 antibody (Ki-67 antigen). The PI was evaluated in three high-power fields (0.1 square millimeter) in the area with the highest proliferative activity. The correlations were calculated according to Spearman-Rho. RESULTS Men were more often surgically treated in the head and neck than women (p < 0.02). Plexiform neurofibromas were more frequently operated on in the head and neck than in other regions (p < 0.01). Older patients were more often treated for the diffuse cutaneous type of neurofibromas (p < 0.0001). The type of tumor did not differ from primaries to recurrent tumors. The MIB- 1 PI showed no association with any of the clinical parameters. In particular, there was no difference of the MIB-1 index between primaries and recurrent tumors. CONCLUSIONS This study showed, for the first time, that proliferation in neurofibromas is not enhanced in previously partially resected neurofibromas. Hence, the argument that trauma or surgery for neurofibromas might promote proliferation, especially in the plexiform neurofibroma, is not supported by the results of the present study. Further this analysis demonstrated interdependencies between tumor type, localisation, age and gender indicative of the social difficulties encountered by the NF1 patients which may be helpful for the advising practitioner.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009455 Neurofibroma A moderately firm, benign, encapsulated tumor resulting from proliferation of SCHWANN CELLS and FIBROBLASTS that includes portions of nerve fibers. The tumors usually develop along peripheral or cranial nerves and are a central feature of NEUROFIBROMATOSIS 1, where they may occur intracranially or involve spinal roots. Pathologic features include fusiform enlargement of the involved nerve. Microscopic examination reveals a disorganized and loose cellular pattern with elongated nuclei intermixed with fibrous strands. (From Adams et al., Principles of Neurology, 6th ed, p1016) Neurofibromas
D009456 Neurofibromatosis 1 An autosomal dominant inherited disorder (with a high frequency of spontaneous mutations) that features developmental changes in the nervous system, muscles, bones, and skin, most notably in tissue derived from the embryonic NEURAL CREST. Multiple hyperpigmented skin lesions and subcutaneous tumors are the hallmark of this disease. Peripheral and central nervous system neoplasms occur frequently, especially OPTIC NERVE GLIOMA and NEUROFIBROSARCOMA. NF1 is caused by mutations which inactivate the NF1 gene (GENES, NEUROFIBROMATOSIS 1) on chromosome 17q. The incidence of learning disabilities is also elevated in this condition. (From Adams et al., Principles of Neurology, 6th ed, pp1014-18) There is overlap of clinical features with NOONAN SYNDROME in a syndrome called neurofibromatosis-Noonan syndrome. Both the PTPN11 and NF1 gene products are involved in the SIGNAL TRANSDUCTION pathway of Ras (RAS PROTEINS). Peripheral Neurofibromatosis,Recklinghausen Disease of Nerve,von Recklinghausen Disease,Cafe-au-Lait Spots with Pulmonic Stenosis,Molluscum Fibrosum,NF1 (Neurofibromatosis 1),Neurofibromatosis I,Neurofibromatosis Type 1,Neurofibromatosis Type I,Neurofibromatosis, Peripheral Type,Neurofibromatosis, Peripheral, NF 1,Neurofibromatosis, Peripheral, NF1,Neurofibromatosis, Type 1,Neurofibromatosis, Type I,Pulmonic Stenosis with Cafe-au-Lait Spots,Recklinghausen Disease, Nerve,Recklinghausen's Disease of Nerve,Recklinghausens Disease of Nerve,Watson Syndrome,von Recklinghausen's Disease,Cafe au Lait Spots with Pulmonic Stenosis,Neurofibromatoses, Peripheral,Neurofibromatoses, Type I,Neurofibromatosis, Peripheral,Peripheral Neurofibromatoses,Pulmonic Stenosis with Cafe au Lait Spots,Syndrome, Watson,Type 1 Neurofibromatosis,Type 1, Neurofibromatosis,Type I Neurofibromatoses,Type I, Neurofibromatosis,von Recklinghausens Disease
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths

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