Abstract

Abstract Podoplanin (PDPN) is a biomarker for poor prognosis in head and neck squamous cell carcinoma (HNSCC). A prospective study was designed to investigate the prognostic value of circulating tumor cells (CTCs) with PDPN expression (PDPN+-CTCs) in HNSCC patients. Sixty-one healthy donors and fifty-three HNSCC patients with locally advanced and metastatic diseases were enrolled in this study. CTCs were enriched from the peripheral blood by the negative selection method PowerMag that has been validated in our previous study. Enumeration of CTCs was performed by co-immunofluorescence staining using the anti-epithelial cell adhesion molecule (EpCAM) and anti-PDPN antibodies. The CTCs (EpCAM+) and PDPN+-CTCs (EpCAM+PDPN+) counts between the patients and healthy volunteers were statistically different (p < 0.0001). When assessed the progression-free survival (PFS) and overall survival (OS) of the patients, we found that the median PFS for the patient group was 8.6 (95% CI: 4.781-12.419) months and the median OS has not reached 50% after the follow-up duration of 9.1 (5.2-17.1) months. Analysis of the CTCs and PDPN+-CTCs counts revealed that neither of them can be considered as a predictive factor for PFS and OS. Notably, the ratio for the PDPN+-CTCs over total CTCs has progonic value in the assessment of PFS and OS. Based on the ROC curve, the prediction of 6-month death could be revealed at the cutoff value of 20% (AUC: 0.718, sensitivity: 94.7%, specificity: 51.7%, p = 0.011). The patients with PDPN+/EpCAM+-CTCs ratio >20% were associated with poor PFS (hazard ratio (HR): 4.666, 95% CI: 1.373-15.856, p = 0.016) and OS (HR: 12.400, 95% CI: 1.643-93.570, p = 0.015). Kaplan-Meier survival curve further confirmed that the PDPN+/EpCAM+-CTCs ratio had significant impact on PFS (p = 0.006) and OS (p = 0.008). In conclusion, CTCs enumeration clearly differentiates HNSCC patients from healthy individuals, while the PDPN+/EpCAM+-CTC ratio is more important than the absolute CTCs count in determining the degree of malignancy and serves as an independent prognostic factor for PFS and OS. Citation Format: Ching-Ping Tseng, Hung-Chih Lin, Chia-Hsun Hsieh, Hung-Ming Wang, Ju-Chien Cheng. Prognostic value of circulating tumor cells with podoplanin expression in locally advanced and metastatic head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4830. doi:10.1158/1538-7445.AM2014-4830

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