Aneuploidy and high S-phase as biomarkers of poor clinical outcome in poorly differentiated and anaplastic thyroid carcinoma

Abstract

Abstract. This study aimed to investigate the prognostic influence of DNA flow cytometry and RAS gene mutations in patients with poorly differentiated (PDTC) and anaplastic thyroid carcinoma (ATC). The series consisted of 26 patients with PDTC and ATC, and a median follow-up of 10 months (range 1-138). DNA ploidy and S-phase fraction (SPF) were assessed by flow cytometry on frozen samples. RAS point mutations were detected using PCR techniques. Disease staging and tumour angioinvasion were included as prognostic parameters for survival analysis. Nineteen patients (73.1%) succumbed to the disease (median time 5 months; range 1-45). Eighteen tumours (69.2%) were classified as DNA aneuploid. Median SPF was 5.6% (range 1.9-23.1), which was used as a cut-off value to distinguish between low versus high cell proliferation. Three of 20 (15%) patients presented N-RAS gene mutations in codon 61. DNA aneuploidy was most frequently found in female patients (p=0.034). Kaplan-Meier and Cox regression analyses showed that only DNA aneuploidy (p=0.044 and p=0.055, respectively) and high SPF (p=0.001 and p=0.006, respectively) significantly correlated with worse survival. The results indicate that aneuploidy and high SPF are biomarkers of poor clinical outcome in PDTC and ATC, which may provide useful prognostic information with a potentially therapeutic impact in patient management.

Three-Dimensional Telomere Dynamics in Follicular Thyroid Cancer

“…The presence of Thrb PV/PV thyrocyte populations with 40 or more telomere signals in several age groups is consistent with the notion that both aneuploid and/ or tetraploid cells have tumorigenic properties (47)(48)(49). Aneuploidy is common in many human cancers (50,51) and serves as independent prognostic factor for clinical outcome of numerous cancer types, including differentiated and undifferentiated/anaplastic thyroid cancer (52)(53)(54).…”

Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour

“…Therefore, in this work, we studied ploidy essentially for three reasons: i) to test its value as a biomarker of tumour aggressiveness; ii) to gather ploidy information in familial PTC (no data on this issue has been published so far); and iii) to investigate a potential link between shorter telomere length, chromosomal instability and aneuploidy. In thyroid cancer, patients displaying aneuploid tumours are in general associated with decreased survival (26,27). However, as mentioned earlier, the low incidence of aneuploidy is a common finding in sporadic PTC (26), consistent with its mostly indolent course and favourable prognosis.…”

“…DNA ploidy, for better characterisation of tumour biological aggressiveness, are missing. Aneuploidy is a molecular feature that identifies genetic instability, and potentially, higher metastatic capacity, being commonly associated with worse disease prognosis (26,27). In two recent studies of familial PTC, although controversial (28), Capezzone et al observed shorter telomere length in the leukocytes, other non-neoplastic tissues and tumours in the familial cases when compared with patients with sporadic PTC or healthy subjects (29,30).…”

Multi-biomarker pattern for tumor identification and prognosis

“…This method identifies the relative cellular DNA content and its localization in phase S cellular cycle in both fresh-and frozensamples [Pinto et al, 2008]. Although its use as prognostic indicator in breast cancer has been documented, results are inconsistent [Nunez, 2001].…”