Incomplete radiofrequency ablation may elicit pro-oncogenic effects in thyroid cancer cells in a xenograft mouse model

Radiofrequency ablation (RFA) is a safe and effective treatment for benign thyroid nodules and is also considered an alternative option for low-risk papillary cancers. Evaluating the completeness of RFA through ultrasound and cytology can be challenging, highlighting the need to investigate the thermal effects on any residual viable cancer cells. Our objective was to examine the adaptive responses of thyroid cancer cells that survive transient heat stress. Xenograft tumors were established in NOD/SCID mice, and a single session of RFA was administered once the tumors became palpable. For in vitro studies, culture vessels containing papillary thyroid cancer cell lines were briefly submerged in water baths at temperatures of 37, 40, or 42 °C. Functional assays and RNA sequencing were conducted. Following initial volume suppression after RFA, accelerated growth of xenograft tumors was observed. These tumors exhibited higher Ki-67 labeling indices and increased microvessel densities compared to the sham ablation group. Heat treatment at 40–42 °C promoted colony and thyrosphere formation, as well as the migratory and invasive abilities of thyroid cancer cells. The expression levels of HSP90 and HSP70 were upregulated, and treatment with ganetespib, an HSP90 inhibitor, mitigated the promoting effects of heat treatment. Furthermore, heat treatment elevated vascular endothelial growth factor levels and enhanced endothelial cell tube formation. Sublethal heat stress may undesirably potentiate tumor growth and angiogenesis. These findings emphasize the importance of achieving complete tumor destruction. Long-term clinical trials are needed to monitor the safety of RFA for thyroid cancer.