Lack of prognostic impact of p53 gene mutation and p53 phosphorylation at serine 15 in multimodally treated adenocarcinomas of the gastroesophageal junction.
OBJECTIVE
As inactivation of p53 may be correlated with poor response of tumors to chemo- and/or radiotherapy the presence of p53 mutations in exons 5-8 was determined in adenocarcinomas of the gastroesophageal junction (GEJ). As p53 protein phosphorylation at serine 15 indicates stabilization and protection against mdm-2 the presence of this phosphorylation state was subsequently evaluated.


METHODS
Mutations in exons 5-8 were analyzed by denaturing high pressure liquid chromatography (DHPLC) and subsequent sequence analysis in pretherapeutic biopsies of 38 adenocarcinomas of the GEJ that had undergone multimodal treatment in the course of a prospective multicentric phase III trial. The presence of p53 protein phosphorylation at serine 15 was evaluated by immunohistochemistry.


RESULTS
Mutations in the DNA binding region were found in 23 samples and were only weakly associated with worse 2-year survival (P=0.083). Phosphorylation at serine 15 of p53 was detected in 14 samples, being neither associated with p53 mutation nor with patient's survival.


CONCLUSIONS
This allows the conclusion that the determination of these two parameters does not help to select patients who do profit from multimodal treatment for adenocarcinomas of the GEJ.
Institute of Pathology, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
Franziska
F
Pühringer-Oppermann
Michael
M
Stahl
Gisela
G
Keller
Mario
M
Sarbia
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D004943:Esophagogastric Junction; D016158:Genes, p53; D006801:Humans; D015337:Multicenter Studies as Topic; D009154:Mutation; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D012694:Serine; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D012694:Serine