Allelic loss of 3 different tumor suppressor gene loci in benign and malignant endothelial tumors of the head and neck.
BACKGROUND
Angiosarcomas are rare malignancies that commonly arise in the head and neck. No definitive precursor lesion or etiological link between hemangiomas and angiosarcoma has been postulated. Evidence at the cell culture level suggests that loss of heterozygosity of 13q might be involved in tumorigenesis of endothelial cells. Although overexpression of p53 and WT-1 has been found in angiosarcoma, little is known about the molecular changes involved.


OBJECTIVE
This study compared the molecular profile of angiosarcoma with that in some benign vascular lesions.


METHODS
Specimens from 6 cases of angiosarcoma, 5 of hemangioma, and 5 of granulation tissue were microdissected. DNA extraction and polymerase chain reaction amplification for 11 microsatellite markers on chromosomes 11p13, 13q14, and 17p13 (WT-1, RB, p53) were performed. Loss of heterozygosity of amplification products was assessed by capillary electrophoresis. Allelic loss and fractional allelic loss were calculated.


RESULTS
The mean fractional allelic loss was 43% for angiosarcomas and 29% for hemangiomas. Eighty-three percent of angiosarcomas had allelic loss at 17p13, 66% at 13q14, and 50% at 11p13. Allelic loss was seen in 60% of hemangiomas at 13q14 and 17p13, but only in 20% at 11p13. Two cases of hemangioma and all the granulation tissue cases had no allelic losses.


CONCLUSIONS
In our study, 11p13, 13q14, and 17p13 allelic losses were present in both hemangiomas and angiosarcomas. This supports the cell culture-based theories that tumorigenesis in endothelial cells likely involves these chromosomes and provides some insight into the potential pathogenesis of angiosarcomas and benign hemangiomas.
Domfeh
Akosua B
AB
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pa, USA.
Fichera
Michelle
M
Hunt
Jennifer L
JL
D002880:Chromosomes, Human, Pair 11; D002882:Chromosomes, Human, Pair 13; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000032:analysis; D004730:Endothelium, Vascular / Q000473:pathology; D016161:Genes, Retinoblastoma; D016147:Genes, Tumor Suppressor; D016162:Genes, Wilms Tumor; D016158:Genes, p53; D005819:Genetic Markers; D006097:Granulation Tissue / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006391:Hemangioma / Q000235:genetics* / Q000473:pathology; D006394:Hemangiosarcoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D042282:Microdissection; D018895:Microsatellite Repeats / Q000235:genetics
D004273:DNA, Neoplasm; D005819:Genetic Markers