Microsatellite analysis of recurrent vestibular schwannoma (acoustic neuroma) following stereotactic radiosurgery.
OBJECTIVE
Genetic and immunohistochemical studies may provide insight into the mechanisms of vestibular schwannoma (VS) recurrence following radiation therapy.


BACKGROUND
Stereotactic radiation therapy is an increasingly common alternative to microsurgical resection for the primary management of sporadic VS. The molecular mechanisms associated with recurrent vestibular schwannoma (VS) following radiation therapy are not known.


METHODS
Primary or irradiated VS tumors were fresh-frozen at the time of surgical resection and microdissected to undergo DNA extraction. Lymphocytic control DNA was isolated from blood obtained by venipuncture. Paired normal and tumor DNA specimens were analyzed for allelic loss by PCR amplification of polymorphic dinucleotide repeat sequences. Immunohistochemical studies were performed on paraffin-embedded, irradiated surgical specimens.


RESULTS
Using 16 polymorphic microsatellite markers, 20 of 26 non-irradiated VS demonstrated loss of heterozygosity (LOH) in at least one locus of chromosome 22q. In contrast, none of the four irradiated recurrent VS demonstrated LOH on chromosome 22q (p = 0.008). No allelic loss was seen in either the primary or irradiated VS utilizing markers mapping to chromosome 10. Deletions on chromosome 10 are seen in both benign and higher-grade meningiomas and intracranial malignancies associated with radiotherapy. Immunohistochemical studies were performed to detect the protein product of the NF2 gene, merlin, in the four irradiated VS. NF2 staining was not observed.


CONCLUSIONS
This study represents the first microsatellite and immunohistochemical analysis of recurrent VS following radiation therapy. Our preliminary observations suggest an alternative mechanism of NF2 inactivation that may correlate with radioresistance in VS.
Lee
Daniel J
DJ
Department of Otolaryngology, UMass Memorial Medical Center, Worcester, MA 01655, USA. djlee@massmed.org
Maseyesva
Brett
B
Westra
William
W
Long
Donlin
D
Niparko
John K
JK
Califano
Joseph
J
D001483:Base Sequence; D016009:Chi-Square Distribution; D002879:Chromosomes, Human, Pair 10; D002892:Chromosomes, Human, Pair 22; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D025581:Neurofibromin 2 / Q000032:analysis / Q000235:genetics; D009464:Neuroma, Acoustic / Q000235:genetics* / Q000378:metabolism / Q000601:surgery*; D016634:Radiosurgery
D004273:DNA, Neoplasm; D025581:Neurofibromin 2