Genetic alterations involved in the development of gallbladder carcinomas from Greek patients.
OBJECTIVE
The genetic pathways of gallbladder cancer are not yet well defined since the contribution of genetic abnormalities clarified in other organs remains questionable.


METHODS
We investigated a group of 22 gallbladder carcinomas from Greek patients with regard to p53 mutations, bax and TGF-beta RII alterations--as indicators of microsatellite instability. The findings were correlated to the presence of ras mutations, patients' clinicopathologic features and survival. PCR-SSCP analysis was performed for the detection of p53 mutations in conserved domains IV and V.


RESULTS
In five tumors p53 mutations were detected; none of them was ras mutated. Although these tumors were characterized by flat morphology, low histologic grade and rather advanced stage, no statistical correlation could be determined. No indications of microsatellite instability were found.


CONCLUSIONS
Ras and p53 genes do not appear to cooperate during gallbladder cancer, at least as far as the flat type of cancer is concerned. p53 alterations are likely to take part in the de novo pathway of gallbladder carcinogenesis.
Saetta
A
A
Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. asaetta@cc.uoa.gr
Lazaris
A C
AC
Michalopoulos
N V
NV
Davaris
P S
PS
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D005260:Female; D005704:Gallbladder / Q000473:pathology; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006115:Greece; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018125:Receptors, Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II