Molecular and Cellular Pathology
British Journal of Cancer (2002) 86, 886–892. doi:10.1038/sj.bjc.6600133 www.bjcancer.com
Published online 18 March 2002
Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory protein, in pancreatic adenocarcinoma
A I Sarela1,3, C S Verbeke4, J Ramsdale4, C L Davies1,2, A F Markham2 and P J Guillou1,3
- 1Academic Unit of Surgery, School of Medicine, University of Leeds, Leeds, UK
- 2Academic Unit of Molecular Medicine, School of Medicine, University of Leeds, Leeds, UK
- 3Department of General Surgery, St James's University Hospital, Leeds LS9 7TF, UK
- 4Pathology, St James's University Hospital, Leeds LS9 7TF, UK
Correspondence: PJ Guillou, E-mail: p.j.guillou@leeds.ac.uk
Received 3 December 2001; Accepted 4 December 2001.
Abstract
Survivin is unique for its expression in human malignancies but not in normal adult cells. It has been implicated in sensitisation to chemotherapy and as a prognostic marker in several common cancers. Immunohistochemistry for Survivin, P53 and BCL-2 expression as well as cell proliferative index (Ki-67) and apoptosis index (TUNEL) was conducted on 52 pancreatic and 12 ampullary adenocarcinomas. Survivin was detected in the cytoplasm of carcinoma cells in 46 (88%) of pancreatic tumours. P53 and BCL-2 were detected in 54% and 12% of pancreatic tumours, respectively. Proliferative index was 26.2
10.5% and apoptosis index was 1.38
0.69%. Prevalence of Survivin expression was significantly higher in P53-positive than in P53-negative cases (P=0.05) but was not associated with BCL-2 expression. Incrementally higher weighted scores of Survivin expression were associated with increased proliferative index (P=0.001). Furthermore, there was linear correlation between increased proliferative index and higher apoptosis index (P<0.001). Surprisingly, higher scores of Survivin expression were associated with increased apoptosis index (P=0.007). Survival characteristics were not influenced by Survivin, P53 or BCL-2 expression, apoptosis index or proliferative index. Ampullary carcinoma showed Survivin expression in 83% of cases. However, unlike pancreatic carcinoma, there was no correlation between Survivin and P53 expression or proliferative index. In conclusion, Survivin is expressed in the majority of pancreatic adenocarcinomas and correlates with both cellular proliferation and apoptosis. Molecular manipulation of Survivin expression may enhance chemotherapy and radiation therapy for pancreatic cancer.
Keywords:
pancreatic neoplasms, inhibitor of apoptosis, P53, BCL-2
