Correlation between transcriptional expression of survivin isoforms and clinicopathological findings in human colorectal carcinomas

Survivin, a novel member of the inhibitor of apoptosis protein (IAP) family, has been markedly overexpressed in most types of human carcinoma, and recognized as a potential target in anticancer therapy. In addition, two splice variants of survivin, survivin-2B and survivin-deltaEx3, have recently been identified. However, expression analysis on its splice variants has not been reported in colorectal carcinomas. Therefore, we investigated the transcription levels of survivin and its splice variants in human colorectal carcinomas, and the correlation between transcript expression levels and pathological findings was analyzed. Tumor tissue samples were provided from 52 cases with colorectal adenocarcinoma resected at the Osaka Medical College from 1995 to 1996. Transcription levels were measured by performing quantitative reverse transcription-polymerase chain reaction (RT-PCR) using primer pairs specific for survivin and either of its splice variants, then normalized by the glyceraldehyde 6-phosphate dehydrogenase. The transcription levels of survivin and its splice variants were significantly higher in the tumor tissue samples, and significantly lower in the normal tissue samples. In addition, approximately 40% of the normal tissue samples did not have any survivin expression. The relative expression level of survivin-2B to survivin (survivin-2B/survivin) was significantly higher in the tumor tissue samples than in the normal ones. In contrast, survivin-deltaEx3/survivin revealed no difference between tumor and normal samples. When Comparing the histological disease stages (stage I and II vs. stage III and IV), there were no significant differences in the expression levels of survivin and its splice variants. The expression level of survivin-2B/survivin for stage Ill and IV was lower than the one for stage I and II. In addition, a higher level of survivin-2B/survivin significantly correlated with a better prognosis in the present series. The present study demonstrates high expression level of survivin and its splice variants, which is relatively specific in tumor tissue and suggests that they have important roles in the progression of human colorectal carcinomas.