The quest for reliable biomarkers: circulating free DNA in thyroid cancer

Jumaah i Al; Shailesh Gohil; Narendra Reddy; Jacqui Shaw; Levy Miles J

doi:10.1530/endoabs.110.EP1495

JOINT733

Introduction: Thyroid cancer (TC) is the most common endocrine malignancy. The overall 5-year survival is in excess of 85%, especially in well-differentiated papillary type. Despite the very good prognosis, 20% of patients would have recurrence. Currently, surveillance consists of serial thyroglobulin, calcitonin and CEA, imaging and biopsies. All of which have limitations from poor sensitivity to risk of malignancy and invasiveness. Circulating Cell-free DNA (cfDNA) is a liquid biopsy that detects circulating DNA fragments in plasma. It is simple, non-invasive and has shown promising results in other cancers, such as breast and colon.

Aim and Objectives: We hypothesise that cfDNA can be used as a surveillance tool in TC, by plotting serial cfDNA levels against the clinical course of TC.

Methods: Eighty-two plasma samples were collected from 23 patients during follow up at different stages of TC (pre-op, post-op, post RI/chemo, remission, stable disease, residual disease, progression/mets). cfDNA was extracted using QIAamp® circulating NA kit (Qiagen). Total cfDNA and fragment length distribution was determined using 4200 TapeStation (Agilent Technologies).

Results: Participants characteristics are summarised in table 1. The lowest cfDNA concentration was 87ng/ml and the highest was 1430ng/ml. The mean value of cfDNA in each stage of the disease is shown in tablet 2. Papillary TC produced mean cfDNA concentration of 276.4ng/ml, compared to in 230.4ng/ml Follicular, 232.2ng/ml in Medulary and 298.2ng/ml in Anaplastic type. Interestingly, the highest cfDNA concentration was extracted from post-op plasma sample and the 2^nd highest was from plasma sample taken during remission.

Table 1: Participants and tumour characteristics *TC: Thyroid Cancer*.
Gender
Male	14
Female	9
Age at recruitment	Average in years
Male	55
Female	54
TC type
Papillary TC	12
Follicular TC	5
Medullary TC	3
Anaplastic TC	3
Metastases at recruitment (Local and distant)
Yes	13
No	10

Table 2: Average cfDNA concentration in various stages of TC.
Disease Stage	Number of cfDNA Samples	Average Concentration(ng/ml)
Pre-op	8	204.3
Post-op	16	256.3
Post RI/Chemo	14	203.5
Remission	17	286.7
Residual disease	8	251.3
Stable known disease	4	231.25
Progression/Mets	15	300.4

Discussion: Our results showed that cfDNA levels did not track disease activity although cfDNA was detected in patients with anaplastic and poorly-differentiated TC. The role of cfDNA in non-aggressive tumours without metastases is less clear and larger-scale studies are required to examine cfDNA role in surveillance of TC.

Endocrine Abstracts

EP1495