PP22-3 Circulating Tumor Cells (CTCs) in Metastatic Papillary Thyroid Cancer:  Report of a Case-Control Pilot Study

Program: Abstracts - Orals, Poster Previews, and Posters
Session: SAT 270-310-Thyroid Neoplasia (posters)
Clinical/Translational
Saturday, April 2, 2016: 1:15 PM-3:15 PM
Exhibit/Poster Hall (BCEC)

Poster Board SAT 300
Jian Yu Xu*1, Tanweer Zaidi2, Gilbert J Cote1, Mimi I-Nan Hu1, Steven G Waguespack1, Maria E Cabanillas1, Anita K Ying1, Naifa L Busaidy3, Mouhammed Amir Habra1, Namita Shanbhag2, Duy Truong4, Robert K. Yu2, Sanjay Shete2, Ruth L. Katz2 and Steven I Sherman1
1The University of Texas MD Anderson Cancer Center, Houston, TX, 2THE UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER, HOUSTON, TX, 3MD Anderson Cancer Center, Houston, TX, 4THE UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER
Background: Enumeration of circulating tumor cells (CTCs) in metastatic papillary thyroid cancer (MPTC) patients has been unsuccessful, when based on EpCAM assays that fail to capture CTCs. To overcome this, we designed an antigen-independent FISH based assay using DNA probes that had previously been used to detect lung cancer CTCs. We hypothesized that these probes might detect CTCs in PTC, as both lung and thyroid are derived from foregut endoderm and associated with NKX2-1/TTF1, a lineage-survival oncogene, which controls expression of genes such as surfactant proteins (SFPT) associated with differentiation in lung and thyroid progenitor cells.

Objectives: To evaluate the presence of CTCs in peripheral blood of patients with MPTC, we tested patients with MPTC and controls, attempting to establish a new prognostic /surrogate marker of disease progression and response to therapy. We also wished to see if the lung cancer probe set could accurately detect CTCs of MPTC.

Patients and Methods: We recruited 12 MPTC patients (aged 62±15.7 years) and 8 control patients (aged 46.9±12.1 years) with history of PTC, total thyroidectomy and disease-free (NED) for ≥5 years. Thirty healthy subjects with absence of known thyroid and lung cancer (aged 62.7±7.8 year) were included as a second control group. Peripheral blood mononuclear cells were isolated and hybridized with a multi-color cocktail of 4 DNA probes:  2 locus specific probes at 10q22 (SFTPA1, 2) and 3p22, and 2 centromeric probes, CEP10 and CEP3. A scanning system scored fluorescent signals on a per cell basis on 500 cells. Signal patterns were independently analyzed by 2 readers into distinct classes: CTCs (cells with gains of ≥2 probes), deletions or gains (loss or gain of a single probe), and normal cells.

 

Results: Patients with MPTC had higher CTCs (0.9±0.3, P<0.001 and 99.9% power) than patients with NED (0.18±0.18) or healthy controls (0.18±0.23). The cutoff of 0.6% CTC (3/500 cells) differentiated between MPTC and controls from both groups. Compared with healthy controls, patients with MPTC had higher percentages of deletion of CEP 3 (0.80±0.85 vs 0.19±0.53, P=0.006), CEP10 (1.43±1.37 vs 0.45±0.67, P=0.002), gain of CEP10 (0.45±0.34 vs 0.23±0.28, P=0.03) and gain of 10q22.3 (0.77±0.60 vs 0.13±0.17, P<0.001), deletions and gains (5.68±1.91 vs 2.47±1.27, P<0.001) and decreased percentage of normal cells (94.33±1.88 vs 97.52 ±1.24, P<0.00001).

Conclusion: Blood from MPTC patients demonstrated CTCs characterized by aneuploidy, with higher levels of CTCs compared with controls. The probes designed for lung cancer were successful in detecting genetic aberrations in MPTC patients’ CTCs, possibly resulting from similar lineage-specific chromosomal changes in lung and thyroid malignant progenitor cells. Studies with larger cohorts are needed to confirm the significance of CTCs as a prognostic marker for MPTC.

Nothing to Disclose: JYX, TZ, GJC, MINH, SGW, MEC, AKY, NLB, MAH, NS, DT, RKY, SS, RLK, SIS

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting/pr-resources-for-endo

Sources of Research Support: Endocrine Fellows Foundation Grant awarded to JYX.