Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory protein, in pancreatic adenocarcinoma

A I Sarela, C S Verbeke, J Ramsdale, C L Davies, A F Markham, P J Guillou, A I Sarela, C S Verbeke, J Ramsdale, C L Davies, A F Markham, P J Guillou

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.

Copyright 2002 Cancer Research UK

Figures

Figure 1
Figure 1
Immunohistochemistry for Survivin, P53, BCL-2, Ki-67 and apoptosis (TUNEL assay) on pancreatic carcinomas. (A) Carcinomatous glands show strong cytoplasmic expression of Survivin whereas normal duct epithelium and stromal cells are negative (200×). (B) Endocrine cells of Langerhans islets show strong Survivin expression (100×). (C) Strong nuclear immunostaining for P53 is seen in neoplastic cells only (200×). (D) BCL-2 immunostaining is negative in neoplastic glands. Tumour-infiltrating lymphocytes show strong BCL-2 expression (100×). (E) Ki-67 immunostaining reveals high proliferative activity in neoplastic glands whereas only few positive cells are found in normal duct epithelium (200×). (F) TUNEL assay detects an apoptotic body flanked by an early apoptotic cell in a neoplastic gland (200×).
Figure 2
Figure 2
Distribution of weighted scores for Survivin expression in pancreatic and ampullary cancers.
Figure 3
Figure 3
Increasing proliferative indices correlate significantly with rising weighted scores for Survivin expression in pancreatic cancers (P=0.001).
Figure 4
Figure 4
Significant positive correlation between proliferative and apoptosis indices in pancreatic cancers (P<0.001).
Figure 5
Figure 5
Increasing apoptosis indices correlate significantly with rising weighted scores for Survivin expression in pancreatic cancers (P=0.007).
Figure 6
Figure 6
Kaplan–Meier analysis of survival following pancreaticoduodenectomy for pancreatic cancer.

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