Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory protein, in pancreatic adenocarcinoma.
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.
Sarela
A I
AI
Academic Unit of Surgery, School of Medicine, University of Leeds, Leeds, UK.
Verbeke
C S
CS
Ramsdale
J
J
Davies
C L
CL
Markham
A F
AF
Guillou
P J
PJ
D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D016159:Tumor Suppressor Protein p53