Expression of survivin messenger RNA correlates with poor prognosis in patients with hepatocellular carcinoma.

Suppression of apoptosis is important for carcinogenesis and tumor growth. Recent studies revealed that survivin not only inhibited apoptosis but also accelerated cancer cell proliferative activity. To investigate the prognostic role of expression of the antiapoptosis gene, survivin, in hepatocellular carcinoma (HCC), the authors analyzed the correlation between the expression pattern of survivin messenger RNA (mRNA) and clinicopathologic findings of patients. Tissues were obtained by surgical resection of livers from 51 patients with HCC and 6 patients without HCC. Expression of survivin mRNA was evaluated using reverse transcription-polymerase chain reaction in 51 tumors, 51 adjacent histologically noncancerous livers, and 6 normal livers. Survivin protein expression was evaluated using Western blotting, and apoptotic cancer cells were detected by immunostaining with polyclonal rabbit anti-single-stranded DNA. Survivin mRNA expression was detected in 21 of 51 (41%) tumors, 2 of 51 (4%) noncancerous livers, and none of the 6 normal livers. Survivin mRNA expression did not correlate with tumor size or stage of HCC. Percentage of apoptotic cancer cells of 30 survivin mRNA-negative tumors (5.2 +/- 3.4%) was significantly higher than that of 21 survivin mRNA-positive tumors (2.2 +/- 2.3%, P = 0.0019). The disease-free 5-year survival rate of 21 patients positive for survivin mRNA (19%) was significantly poorer than that of 30 patients negative for survivin mRNA (39%, P = 0.0148). Survivin mRNA was detected in 57% (17/30) patients with HCC recurrence but in only 19% (4/21) of patients without recurrence (P = 0.0072). These results indicated that survivin mRNA expression could be used as an independent prognostic factor for patients with HCC after hepatectomy.