CK19 mRNA expression measured by reverse-transcription polymerase chain reaction (RT-PCR) in the peripheral blood of patients with non-small cell lung cancer treated by chemo-radiation: An independent prognostic factor

Abstract

To investigate the prognostic significance of circulating cancer cells in peripheral blood (PB) of patients with non-small cell lung cancer (NSCLC) treated by chemo-radiation with curative intent. Cytokeratin-19 (CK19) mRNA was measured by nested reverse-transcription polymerase chain reaction (RT-PCR) in PB from 67 NSCLC patients before and after chemo-radiation. The measurements of CK19 mRNA were compared to the outcome of therapy to evaluate its significance of prognoses. The sensitivity and specificity of CK19 RT-PCR was 10(-7) and 96.7%, respectively. The positive rate of CK19 mRNA in PB before chemo-radiation was correlated only to N stage (p=0.014). In contrast, it was more closely correlated to histological types (adenocarcinoma versus non-adenocarcinoma) (p=0.019), weight loss (p=0.010), KPS status (p=0.027) and N stage (p=0.032) after chemo-radiation. CK19 status in PB before chemo-radiation did not permit predictions of overall survival (p=0.375) and progression-free survival (p=0.573). However, the patients with CK19 mRNA expression in PB after treatments had poorer overall survival (p<0.001) and progression-free survival (p<0.001) as compared to those with negative CK19 mRNA expression. The worst survivals were seen in patients with persistently positive CK19 mRNA expression both before and after treatments. Multivariate analyses demonstrated that the positivity of CK19 mRNA after chemo-radiation was an independent unfavorable prognostic factor for both overall survival and progression-free survival (p<0.001 and <0.001). Only after chemo-radiation could the measurement of CK19 mRNA in PB predict the prognoses of NSCLC. Patients with the positive CK19 mRNA had shorter survival compared to the negative patients.