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

P Tanière; G Martel-Planche; J C Saurin; C Lombard-Bohas; F Berger; J Y Scoazec; P Hainaut

doi:10.1054/bjoc.2001.1990

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

Br J Cancer. 2001 Sep 1;85(5):721-6. doi: 10.1054/bjoc.2001.1990.

Authors

P Tanière¹, G Martel-Planche, J C Saurin, C Lombard-Bohas, F Berger, J Y Scoazec, P Hainaut

Affiliation

¹ Molecular Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert Thomas, Lyon cedex, 69372 08, France.

Abstract

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.

MeSH terms

Aged
Aged, 80 and over
Carcinoma, Squamous Cell / epidemiology
Carcinoma, Squamous Cell / genetics*
Cell Cycle Proteins / metabolism
Cyclin E / metabolism
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
Cyclin-Dependent Kinase Inhibitor p27
Cyclooxygenase 2
DNA Mutational Analysis
DNA-Binding Proteins
Esophageal Neoplasms / epidemiology
Esophageal Neoplasms / genetics*
Female
France / epidemiology
Gene Amplification
Genes, Tumor Suppressor
Genes, p53 / genetics*
Humans
Incidence
Isoenzymes / metabolism
Male
Membrane Proteins*
Middle Aged
Mutation / genetics*
Neoplasm Proteins / genetics*
Neoplasm Proteins / metabolism
Neoplasm Staging
Nuclear Proteins*
Phosphoproteins / genetics*
Phosphoproteins / metabolism
Prostaglandin-Endoperoxide Synthases / metabolism
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-mdm2
Trans-Activators / genetics*
Trans-Activators / metabolism
Transcription Factors
Tumor Suppressor Proteins*

Substances

CKAP4 protein, human
Cell Cycle Proteins
Cyclin E
Cyclin-Dependent Kinase Inhibitor p16
DNA-Binding Proteins
Isoenzymes
Membrane Proteins
Neoplasm Proteins
Nuclear Proteins
Phosphoproteins
Proto-Oncogene Proteins
TP63 protein, human
Trans-Activators
Transcription Factors
Tumor Suppressor Proteins
Cyclin-Dependent Kinase Inhibitor p27
Cyclooxygenase 2
PTGS2 protein, human
Prostaglandin-Endoperoxide Synthases
MDM2 protein, human
Proto-Oncogene Proteins c-mdm2