Tumour cells of extramammary Paget's disease do not show either p53 mutation or allelic loss at several selected loci implicated in other cancers.
Extramammary Paget's disease is a particular form of skin cancer of unknown histogenesis. To look for the genetic defects underlying the pathogenesis of this tumour, we have examined loss of heterozygosity (LOH), p53 and human papillomavirus (HPV) status, and the expression of c-erbB-2 and bcl-2 proteins in 14 cases. Unexpectedly, no LOH was detected at several loci commonly lost in other human cancers (namely 3p, 9p, 9q, 13q, 16q, 17p, and 17q) in 12 tumours examined. Altered p53 protein expression was entirely or mostly negative in all 14 cases. Direct sequencing of exons 5-8 of the p53 gene in eight cases revealed no mutation. Polymerase chain reaction amplification of the L1 gene of human papillomavirus (HPV) did not detect the virus that could inactivate p53 and retinoblastoma tumour-suppressor gene products. As expected, c-erbB-2 proto-oncogene protein was overexpressed in six cases. The expression of bcl-2 was negative in all cases. The results presented in this study suggest that molecular events underlying extramammary Paget's disease differ from those of other common epithelial malignancies and that tumour-suppressor genes located in chromosome regions not examined in this study may be important.
Takata
M
M
Department of Dermatology, Kanazawa University School of Medicine, Japan.
Hatta
N
N
Takehara
K
K
D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010145:Paget Disease, Extramammary / Q000235:genetics* / Q000473:pathology; D027383:Papillomaviridae / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D012878:Skin Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016159:Tumor Suppressor Protein p53