Analysis of p53 mutations and the expression of p53 and p21WAF1/CIP1 protein in 15 cases of sebaceous carcinoma of the eyelid.
OBJECTIVE
The purpose of this study was to detect mutation of the p53 gene, to assess its relationship with p53 or p21(WAF1/CIP1) expression, and to evaluate the correlation between p53 mutation or p21(WAF1/CIP1) expression and clinicopathologic findings in sebaceous carcinoma of the eyelid.


METHODS
Fifteen conventional paraffin-embedded samples of sebaceous carcinoma of the eyelid were analyzed. Using the single-strand conformation polymorphism technique, the authors sequenced coding exons 5-8 of the p53 gene. The expression of p53 and p21(WAF1/CIP1) protein was analyzed by immunohistochemistry.


RESULTS
In 10 of the 15 cases (66.7%), point mutations were detected in the p53 gene. CC to TT double-base changes (tandem mutations), which are known to be induced only by UV, were not detected in any of the mutations. Correlations between p53 mutation and expression were found to be statistically significant (P = 0.007). There was no significant correlation between p53 mutation and clinicopathologic findings or p21(WAF1/CIP1) expression. However, there was a significant inverse correlation between p21(WAF1/CIP1) expression and presence of lymph node metastasis (P = 0.007).


CONCLUSIONS
Among human cancers, sebaceous carcinoma of the eyelid may be one of those showing most frequent mutation of the p53 gene, which may not be caused by exposure to UV. p21(WAF1/CIP1) downregulation may be associated with lymph node metastasis.
Kiyosaki
Kunihiro
K
Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan. kiyosaki@med.oita-u.ac.jp
Nakada
Chisato
C
Hijiya
Naoki
N
Tsukamoto
Yoshiyuki
Y
Matsuura
Keiko
K
Nakatsuka
Kazuo
K
Daa
Tsutomu
T
Yokoyama
Shigeo
S
Imaizumi
Masamoto
M
Moriyama
Masatsugu
M
D018266:Adenocarcinoma, Sebaceous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D005142:Eyelid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012626:Sebaceous Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53