Original Paper TP53 Gene Mutation Status in Pretreatment Biopsies of Oesophageal Adenocarcinoma Has No Prognostic Value P. Soontrapornchai, 1 H. Elsaleh, 1,2 D. Joseph, 2 J.M. Hamdorf, 1 A.K. House 1 and B. Iacopetta 1 1 Department of Surgery, University of Western Australia, Nedlands 6907; and 2 Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia Identi®cation of markers which help to predict response to treatment and overall survival at the time of diagnosis would assist in the management of patients with oesophageal adenocarcinoma. In the present study we investigated the prognostic signi®cance of mutations to the TP53 tumour suppressor gene in a large, consecutive series of oesophageal adenocarcinomas. The incidence of TP53 mutation determined by molecular analysis of endoscopic biopsy specimens was 36% (49/135). No statistically signi®cant diVerence was observed in patient survival according to the TP53 status of the tumour biopsy. The median survival time for patients with mutation was 12  1 months compared with 14  2 months for patients with TP53. These results demonstrate that mutation of the TP53 gene is not a useful predictive marker for patient survival in oesophageal adenocarcinoma. # 1999 Elsevier Science Ltd. All rights reserved. Key words: oesophageal adenocarcinoma, TP53 gene, prognostic marker, biopsy, patient outcome, adjuvant therapy Eur J Cancer, Vol. 35, No. 12, pp. 1683±1687, 1999 INTRODUCTION Oesophageal carcinoma is one of the more aggressive can- cers and has a 5-year survival of less than 10%. It is the sixth most common cancer worldwide [1] and is responsible for more than 600 deaths per year in Australia alone. Adeno- carcinoma is the predominant subtype in Western countries where the incidence and mortality from this cancer have been increasing [2]. De®nitive diagnosis is made by endoscopic biopsy. Because most patients present with late stage disease, surgical resection alone does not greatly extend patient sur- vival. Various pre- and postoperative adjuvant treatment protocols have, therefore, been tried in an attempt to reduce local recurrence and improve survival, although the results remain controversial [3±6]. The identi®cation of markers which predict oesophageal tumour aggressiveness and response to therapy would be of immense help for the management of these cancer patients. More accurate prognostic information obtained by analysis of endoscopic biopsy specimens at the time of diagnosis would be especially useful in determining further treatment. The discovery of mutations to oncogenes and tumour suppressor genes has opened the possibility of using these as novel prognostic markers. Because of its central role in DNA damage repair, the most promising marker so far has been aberration of the TP53 gene [7]. This can be observed using immunohistochemical (IHC) techniques to detect abnormal accumulation of the TP53 protein in tumour cells, although IHC does not always re¯ect the presence of an underlying gene mutation. Polymerase chain reaction (PCR)-based techniques such as single strand conformation polymorphism (SSCP) and denaturing gradient gel electrophoresis (DGGE) have also been widely used to screen for TP53 gene mutation. Relatively few studies have used DNA sequencing to examine the prognostic signi®cance of TP53 mutation because of the tedious nature and expense of this technique. An additional problem with sequencing is the masking of mutant TP53 allele by the wild-type arising from contaminating normal tissue present within all solid tumours. In spite of the variety of techniques used, it is clear that in some tumour types, most notably breast [8, 9] and gastric cancers [10], TP53 alteration European Journal of Cancer, Vol. 35, No. 12, pp. 1683±1687, 1999 # 1999 Elsevier Science Ltd. All rights reserved. Pergamon Printed in Great Britain PII: S0959-8049(99)00172-0 0959-8049/99/$ - see front matter 1683 Correspondence to B. Iacopetta, e-mail: bjiac@cyllene.uwa.edu.au. Received 18 Jan. 1999; revised 10 Jun. 1999; accepted 13 Jul. 1999.