Sporadic TP53 transition mutations in chronic cholecystitis are possibly linked to gallbladder carcinogenesis.
OBJECTIVE
Gallbladder cancers are well known to frequently exhibit TP53 as well as K-ras gene mutations. This study performed a TP53 gene investigation by PCR-SSCP and direct sequencing using both bile supernatants and tissue samples from cholecystectomy specimens lacking gallbladder cancer, in order to investigate gallbladder carcinogenesis.


METHODS
Eighteen out of 294 cases, mainly of cholecystitis, were extracted by screening SSCP of bile supernatants for TP53 mutations, and investigation of their tissue samples both SSCP and direct sequencing.


RESULTS
Non-neoplastic mucosal samples demonstrated shifted bands in 11 cases (61%), and mutations were confirmed in 7 cases (64%). Unexpectedly, no cases showed identical point mutations in both bile and tissue samples. G:C to A:T transitions, thought to be sporadic mutations, predominated (77%).


CONCLUSIONS
Sporadic TP53 transition mutations were demonstrated in non-neoplastic lesions such as severe cholecystitis, indicating an importance for a chronic cholecystitis-carcinoma sequence in gallbladder carcinogenesis.
Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
Nobuyuki
N
Yanagisawa
Kazuya
K
Yamashita
Tatsuru
T
Kuba
Isao
I
Okayasu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002763:Cholecystectomy; D002764:Cholecystitis / Q000235:genetics* / Q000601:surgery; D002908:Chronic Disease; D004273:DNA, Neoplasm / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004273:DNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53