TP53 mutations, amplification of P63 and expression of cell cycle proteins in squamous cell carcinoma of the oesophagus from a low incidence area in Western Europe.
In Europe, high incidence rates of oesophageal squamous cell carcinoma (SCCE) are observed in western France (Normandy and Brittany) and in north-eastern Italy. Analysis of TP53 mutations in tumours from these regions has shown a high prevalence of mutations at A:T basepairs that may result from DNA damage caused by specific mutagens. However, the spectrum of TP53 mutations in regions of low incidence is unknown. We report here TP53 mutation analysis in 33 SCCE collected in Lyon, an area of low incidence. These tumours were also examined for MDM2 and P63 amplification, and for expression of p16(INK4a/CDKN2a), cyclin E, p27(Kipl)and Cox2. TP53 mutations were detected in 36% of the cases (12/33). In contrast with regions of high incidence, the mutation spectrum did not show a high prevalence of mutations at A:T base pairs. P63 was amplified in 5/32 cases tested (15.5%). No amplification of MDM2 was found. Expression studies revealed frequent loss of p16(INK4a/CDKN2a)(46%) and p27(Kipl)(25%) expression, and frequent overexpression of Cyclin E (70%) and Cox2 (42%). Overall, these results indicate that in Europe, SCCE from areas of high and low incidence present a similar pattern of molecular alterations but differ by the type of TP53 mutations.
Tanière
P
P
Molecular Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert Thomas, Lyon cedex, 69372 08, France.
Martel-Planche
G
G
Saurin
J C
JC
Lombard-Bohas
C
C
Berger
F
F
Scoazec
J Y
JY
Hainaut
P
P
D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051546:Cyclooxygenase 2; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D005784:Gene Amplification; D016147:Genes, Tumor Suppressor; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
C081876:CKAP4 protein, human; D018797:Cell Cycle Proteins; D019927:Cyclin E; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2