| Summary: | Abstract The overall estimated risk of recurrence after an apparently complete thyroid cancer resection ranges from <1% to 55%, and the high‐quality pathology report is crucial for proper risk stratification. The neck ultrasound (US) and serum thyroglobulin (Tg) and anti‐Tg antibody (TgAb) assays are the mainstays for Differentiated Thyroid Cancer (DTC) follow‐up. However, the neck US includes a high frequency of nonspecific findings and despite the serum, Tg unmasks the presence of thyrocytes, it is not discriminating between normal and malignant cells. In this study, to improve post‐surgery follow‐up of minimal residual disease in papillary thyroid cancer (PTC) patients, blood‐derived cytology specimens were evaluated for the presence of circulating tumor cells (CTCs). The presence of CTCs of thyroid origin was confirmed by cytomorphological and tissue‐specific antigens analysis (Thyroid Transcription Factor‐1/TTF‐1 and Tg) and proliferative profile (percentage of cells in S‐phase). Our data revealed an unfavorable’ prognostic risk in patients with >5% CTCs (p = 0.09) and with >30% S‐phase cells at baseline (p = 0.0015), predicting ≤1 year relapsing lesion event. These results suggest a new intriguing frontier of precision oncology forefront cytology‐based liquid biopsy.
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