Endocrine Abstracts

Objectives: Genomic instability play a role in cancer development through different mechanisms including chromosome fragility and in particular the altered telomere length (TL). Previous studies showed that the presence of short telomeres in the blood was associated with development of sporadic head and neck, bladder, lung, renal and breast cancer. In thyroid cancer, has been demonstrated that familial form of papillary thyroid cancer (FPTC) has shorter telomeres in blood leukocytes compared to the sporadic form of PTC (NFPTC). Moreover, higher rate of second malignant tumor (SMT) in FPTC has been recently reported, suggesting the impact of genetic background in the cumulative risk of developing SMT in thyroid cancer patients. The aim of this study was to evaluate the association between the presence of shorter telomeres in blood leukocytes and the risk of SMT in PTC patients.

Methods: We retrospectively evaluated 119 PTC patients (43 FPTC and 76 NFPTC) characterized for TL by Telomerase Fluorescence in situ hybridization (FISH) assay on lymphocyte metaphase chromosomes using a fluorescein-conjugated telomere PNA probe.

Results: In our analysis we observed a significantly shorter TL in PTC patients with SMT when compared to PTC patients without SMT (P = 0.0207). We performed the ROC curve analysis to find a cut-off of TL able to predict the risk to develop SMT beyond PTC. Our analysis showed that a TL <0.715 (AUC: 0.6853; AUC CI: 0.5307-0.8398) was significantly associated with the risk to develop SMT in PTC patients. Moreover, we observed that the shorter TL was more frequent in FPTC compared to NFPTC patients (P < 0.0001) and the patients with familial form of PTC developed SMT more frequently than NFPTC patients (20.9% vs 7.9%, P = 0.03).

Conclusions: The chromosome fragility might play an important role in cancer development in thyroid cancer patients. Our study demonstrates that PTC patients with chromosome instability, characterized by shorter telomeres, are more likely to develop SMT beyond thyroid cancer.