Loss of heterozygosity on chromosome 22 in sporadic schwannoma and its relation to the proliferation of tumor cells.
BACKGROUND
Schwannoma is the tumor arising mainly from the cranial and spinal nerves. Bilateral vestibular schwannoma is the hallmark of neurofibromatosis type 2 (NF2). The NF2 gene has been cloned with comprehensive analysis of its mutations in schwannoma. However, most studies focused on vestibular schwannoma. There are differences in proliferation of tumor cell and ultrastructure between vestibular and spinal schwannomas. It is unknown whether genetic alterations in vestibular schwannoma are different from those in non-vestibular schwannoma. We analyzed the loss of heterozygosity (LOH) on chromosome 22 in patients with sporadic schwannoma including vestibular and spinal schwannomas and correlated this genetic alteration with tumor proliferation.


METHODS
In 54 unrelated patients without clinical NF1 or NF2, 36 patients had sporadic vestibular schwannoma, and 18 dorsal spinal root schwannoma. Four highly polymorphic linkage to NF2 gene microsatellite DNA markers (D22S264, D22S268, D22S280, CRYB2) were used to analyze LOH. The proliferative index was evaluated by Ki-67 and proliferative cell nuclear antigen (PCNA) immunostaining. Student's t test was used to analyze the difference of the proliferative index between schwannoma with LOH and that without LOH. The difference of the frequency of LOH in vestibular and spinal schwannomas was investigated by the chi-square test.


RESULTS
Twenty-three schwannomas (42.6%, 23/54) showed allele loss. The frequency of LOH in vestibular schwannoma was significantly higher than that in spinal schwannoma (chi2 = 5.14, P < 0.05). The proliferative index of schwannoma with LOH was significantly higher than that without LOH (tki-67 = 2.97, P = 0.0045; tPCNA = 2.93, P = 0.0051).


CONCLUSIONS
LOH on chromosome 22 is a frequent event in the tumorigenesis of sporadic schwannoma. And, there is a correlation between LOH on chromosome 22 and proliferative activity in schwannoma. The frequency of LOH in vestibular schwannoma is significantly different from that in spinal schwannoma.
Bian
Liu-guan
LG
Department of Neurosurgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China. rj11118@yahoo.com
Sun
Qing-fang
QF
Tirakotai
Wuttipong
W
Zhao
Wei-guo
WG
Shen
Jian-kang
JK
Luo
Qi-zhong
QZ
Bertalanffy
Helmut
H
D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D002892:Chromosomes, Human, Pair 22; D005260:Female; D016515:Genes, Neurofibromatosis 2; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009442:Neurilemmoma / Q000235:genetics* / Q000473:pathology; D009464:Neuroma, Acoustic / Q000235:genetics*; D013120:Spinal Cord Neoplasms / Q000235:genetics*; D013126:Spinal Nerve Roots