S-phase fraction and ploidy as predictive markers in primary disease and recurrence of papillary thyroid carcinoma

Abstract

To investigate the prognostic influence of DNA ploidy and S-phase fraction (SPF) on disease-free (DFS) and overall survival (OS) of patients with primary disease and loco-regional lymph node recurrence of papillary thyroid carcinoma (PTC). A large prospective study with long-term follow-up (median, 117 months). Two series of patients with primary PTC (n = 305) and lymph node recurrence metastasis (LNM) (n = 39) were involved in the study. Patient's age and gender, histological variant, pathological tumour-node-metastasis (pTNM) staging, extrathyroidal extension, vascular and lymphatic invasion and tumour bilateral growth were the clinical and pathological characteristics evaluated. DNA flow cytometry was performed on fresh/frozen surgical tumour samples. Cox regression models were estimated for prognostic analyses. Seventeen (5·6%) primary tumours and five (12·8%) LNMs were aneuploid, while mean SPF was 2·7% and 3·7%, respectively (P = 0·022). High SPF was significantly associated with lymphatic invasion and tall cell and diffuse sclerosing variants. In univariate analysis, all the clinico-pathological variables, but tumour bilateral growth and gender, were significantly correlated with survival. SPF showed borderline significance (P = 0·051) in relation to OS. In multivariate analysis, older age (≥48 years), lymph node spread and high SPF were significantly adverse prognostic factors. Extrathyroidal extension and distant metastasis for OS, as well as tumour size for DFS, were also found as unfavourable prognostic features. In LNM, the Kaplan-Meier curves showed significant differences for older age and DNA aneuploidy (recurrence; P = 0·011). The results indicate that SPF and ploidy can provide additional predictive information in patients with PTC.