survivin messenger RNA expression is a good prognostic biomarker for oesophageal carcinoma

Abstract

Oesophageal squamous cell carcinoma is one of the most malignant tumours. To identify patients with a high risk of recurrence of oesophageal squamous cell carcinoma, we investigated the prognostic significance of survivin mRNA expression in oesophageal squamous cell carcinoma, which has recently been reported to be a good marker for unfavourable prognosis in various tumours. Tumours and non-cancerous epitheliums adjacent to tumours were obtained by surgical resection from 57 patients with oesophageal squamous cell carcinoma. Expression levels of survivin and glyceraldehyde-3-phosphate dehydrogenase mRNA were analysed quantitatively by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The survivin/glyceraldehyde-3-phosphate dehydrogenase ratios of tumours were higher than those of non-cancerous tissues (P=0.0003). Tumour-survivin/glyceraldehyde-3-phosphate dehydrogenase ratio did not correlate with histologic type, lymph node metastasis, and stage of tumours. In 53 surviving patients, the 5-year survival rate of 17 patients with high survivin mRNA expressed oesophageal squamous cell carcinoma (14.1%) was significantly poorer than that of 36 with low survivin mRNA expressed oesophageal squamous cell carcinoma (46.8%, P=0.0018). In these patients, tumour-survivin mRNA expression was recognised as a good marker of cancer recurrence independently from tumour stage. These findings indicate that survivin mRNA expression in oesophageal squamous cell carcinoma may be a good biomarker for identifying patients with high risk of cancer recurrence.

Figure 1

Standard curves for survivin and GAPDH. The plots represent the log of the input amount (log ng of total starting RNA of EC-GI-10; a: 160 ng, b: 80 ng, c: 40 ng, d: 20 ng, e: 10 ng) as the x-axis and threshold cycle (Ct) as the y-axis for survivin and GAPDH.

Figure 2

Amplification curves of survivin and GAPDH in a typical case. Line a: GAPDH of tumour, line b: GAPDH of non-cancerous tissue adjacent to carcinoma, line c: survivin of tumour, and line d: survivin of non-cancerous tissue. The horizontal line at Rn=0.05 is the threshold for detection.

Figure 3

Strong survivin protein expression was detected in nuclei of all cancer cells and weak survivin expression was observed in the cytoplasm by immunostaining with a polyclonal antibody (×100).

Figure 4

Normal esophageal cells in the basal layer show weak survivin protein expression (×100).

Figure 5

The disease-specific survival curves of the 53 surviving patients. The survival curve of 17 with high-survivin/GAPDH ratio-tumours (line b) was significantly lower than that of 36 with low-survivin/GAPDH ratio- tumors (line a). The difference between two survival curves was statistically significant (P=0.0018).