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. 2000 May;46(5):645–650. doi: 10.1136/gut.46.5.645

Expression of the antiapoptosis gene, Survivin, predicts death from recurrent colorectal carcinoma

A Sarela 1, R Macadam 1, S Farmery 1, A Markham 1, P Guillou 1
PMCID: PMC1727921  PMID: 10764707

Abstract

BACKGROUND/AIMS—Inhibition of programmed cell death (apoptosis) is associated with increased tumour aggressiveness, and expression of Survivin, an antiapoptosis gene, in colorectal carcinomas may provide important prognostic information.
PATIENTS/METHODS—Expression of Survivin messenger RNA was evaluated by reverse transcription-polymerase chain reaction in 144 colorectal carcinomas and 86 adjacent histologically normal mucosa samples from patients for whom long term follow up data were available.
RESULTS—Survivin transcripts were detected in a significantly greater proportion of carcinomas (63.5%) than normal mucosa samples (29.1%; p<0.001). The prevalence of Survivin expression was independent of advancing pathological stage. Death due to recurrent cancer following curative resection was predicted independently by tumour expression of Survivin (hazard ratio (HR) 2.60; 95% confidence interval (95% CI) 1.17-5.75) and lymph node metastases (HR 2.38; 95% CI 1.21-4.70). On stage wise analysis, the predictive value of Survivin expression was limited to patients with stage II colorectal carcinomas; those with Survivin negative tumours had a five year survival rate of 94.4% compared with 44.8% for patients with Survivin positive tumours (p=0.004, log rank test).
CONCLUSION—In patients with stage II colorectal carcinomas, Survivin expression provides prognostic information that may have important therapeutic implications.


Keywords: colorectal neoplasia; messenger RNA; polymerase chain reaction; prognosis; survival

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Figure 1  .

Figure 1  

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RT-PCR products of paired samples of normal colonic mucosa (lanes 1, 3, and 5) and colorectal carcinoma (lanes 2, 4, and 6) obtained from three different resection specimens. Lane 7 is a positive control (SW 480 colon cancer cell line) and lane 8 a negative control. Expression of glyceraldehyde-3-phosphate dehydrogenase (G3PDH) confirmed the fidelity of the reverse transcription. In the first pair, neither normal mucosa nor cancer samples expressed Survivin (lanes 1 and 2); in the second pair, only the cancer sample (lane 4) expressed Survivin but not normal mucosa (lane 3); and in the third pair, both normal mucosa and cancer samples (lanes 5 and 6) expressed Survivin.

Figure 2  .

Figure 2  

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Kaplan-Meier survival plot for patients with colorectal carcinoma stratified by TNM stage (I-IV) and displaying standard survival characteristics (p=0.01, log rank test for trend).

Figure 3  .

Figure 3  

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Kaplan-Meier survival plot for patients with curatively resected colorectal carcinomas (stages I, II, and III) stratified according to tumour expression of Survivin. The five year survival rate of patients with Survivin positive tumours was 53.0% compared with that of 77.5% for patients with Survivin negative tumours (p=0.007, log rank test).

Figure 4  .

Figure 4  

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Kaplan-Meier survival plot for patients with curatively resected stage II colorectal carcinoma stratified according to tumour expression of Survivin. The five year survival rate of patients with Survivin positive tumours was 48.3% compared with that of 94.1% for patients with Survivin negative tumours (p=0.001, log rank test).

Figure 5  .

Figure 5  

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Kaplan-Meier survival plot for patients with curatively resected stage III colorectal carcinoma stratified according to tumour expression of Survivin. The five year survival rate of patients with Survivin positive tumours was 49.0% compared with that of 43.4% for patients with Survivin negative tumours (p=0.66, log rank test).

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