Evaluation of cytokeratin-19 mRNA as a tumor marker in the peripheral blood of nasopharyngeal carcinoma patients receiving concurrent chemoradiotherapy

The reverse transcriptase-polymerase chain reaction (RT-PCR) technique is a tool capable of detecting minute quantities of circulating tumor cell-derived transcripts. Nasopharyngeal carcinoma (NPC) is a rapidly growing tumor of epithelial origin and high metastatic potential. The aim of our study is to investigate the clinical value of circulating cytokeratin-19 (CK-19) mRNA detection in NPC patients. Between June 1997 and March 1999, 57 previously untreated, advanced NPC patients without distant metastasis were uniformly treated by concurrent chemoradiotherapy. Peripheral blood samples were collected prospectively before treatment and subjected to a nested RT-PCR assay. Measures were taken to prevent contamination and pseudogene interference. PCR products of positive results were verified by restriction enzyme Hae II and direct sequencing. Under our nested RT-PCR experimental conditions, 33.3% (19/57) clinically nonmetastatic NPC patients had CK-19 mRNA in their blood. The positive detection rates of CK-19 mRNA in the peripheral blood for different stages were 20.0% for stage II, 31.6% stage III and 43.5% stage IV (p = 0.1335). After a median follow-up time of 35 months, 2 patients had recurrences of their primary tumors and 14 developed distant metastases without Iocoregional recurrence. Nine of 19 (47.4%) CK-19 mRNA-positive patients and 5 of 38 (13.2%) CK-19 mRNA-negative patients developed distant metastasis (p = 0.00826). The 3-year metastasis-free survival rates were 49.9% for patients with detectable CK-19 and 85.9% for those with undetectable CK-19 (p = 0.0089, log-rank test). Our data suggest that the presence of CK-19 mRNA in the peripheral blood may be a potential marker of micrometastasis for NPC.