Genetic changes in sweat gland carcinomas.
The molecular pathogenesis of malignant appendageal tumors is poorly understood. Immunohistochemical staining, polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) and sequencing analyses were performed in a mixed group of 21 sweat gland carcinomas. LOH was mostly confined to the chromosome arm 17p. None of the remaining 17 tumors showed LOH at any loci. Nuclear accumulation of p53 protein was observed in 3 tumors, all of which also showed LOH of 17p. One eccrine gland adenocarcinoma showed allelic loss of 17p and a Cys 176 Arg mutation in the p53 gene. The other three tumors that showed LOH of 17p, however, had wild-type p53 genes. A clear transition from benign eccrine poroma to porocarcinoma that was associated with p53 protein stabilization and allelic loss was observed in one tumor. One eccrine porocarcinoma/undifferentiated adnexal carcinoma showed prominent microsatellite instability, probably reflecting an underlying defect in DNA mismatch repair. Overexpression of erbB-2 was observed in three tumors. The low frequencies of LOH and p53 alterations in sweat gland carcinomas contrasted with the multiple genetic defects normally observed in cutaneous squamous cell carcinomas, and may be partly explained by the relative protection of cutaneous appendages from ultraviolet light and other environmental mutagens.
Takata
M
M
Department of Dermatology, Kanazawa University School of Medicine, Japan. takata@med.kanazawa-u.ac.jp
Hashimoto
K
K
Mehregan
P
P
Lee
M W
MW
Yamamoto
A
A
Mohri
S
S
Ohara
K
K
Takehara
K
K
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000032:analysis; D004276:DNA, Satellite / Q000032:analysis; D004439:Eccrine Glands / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D013544:Sweat Gland Neoplasms / Q000235:genetics* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004273:DNA, Neoplasm; D004276:DNA, Satellite; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53