Circulating Myeloid Derived Suppressor Cells Predict Differentiated Thyroid Cancer Diagnosis and Extent.

Circulating Myeloid Derived Suppressor Cells Predict Differentiated Thyroid Cancer Diagnosis and Extent.

Thyroid. 2016 Jan 12;

Authors: Angell TE, Lechner MG, Smith AM, Martin SE, Groshen SG, Maceri D, Singer P, Epstein AL

Abstract
<b>Background:</b> Establishing the pre-operative diagnosis and long-term prognosis of differentiated thyroid cancer (DTC) remain challenging in some patients. Myeloid-derived suppressor cells (MDSC) are tumor-induced cells mediating immune tolerance that are detectable in the peripheral blood of cancer patients. We previously developed a novel clinical assay to detect the phenotypes of two human MDSC subsets in peripheral blood, and hypothesize that higher MDSC levels measured by this assay correlate positively with both malignancy and worse patient outcomes. <b>Methods:</b> We performed a prospective observational pilot study of patients undergoing thyroidectomy for a solitary thyroid nodule. The presence of a thyroid nodule greater >1cm was confirmed sonographically and fine needle aspiration biopsy performed in all cases. Peripheral blood collected pre-operatively was analyzed using a novel flow cytometry-based immunoassay to detect and quantify two subsets of human MDSC. Circulating MDSC levels were compared by histopathologic diagnosis, stage, and presence of persistent disease after treatment. <b>Results:</b> Of 50 patients included in this study, MDSC measurement was successful in 47 (94%). One patient was found to have a concurrent renal cell carcinoma after data acquisition leaving 46 patients for primary analysis. Final histopathology was benign in 11 (24%) and DTC in 35 (76%), encompassing 34 PTC cases and one follicular thyroid carcinoma. Mean percentages of granulocytic CD11b⁺HLA-DR^lowHIF1a⁺ MDSC (CD11b⁺MDSC) were 14.0%±6.2% and 7.9%±3.6%, in DTC versus benign nodules, respectively (P<0.005). A cut-off of 12% yielded a specificity of 0.91, a sensitivity of 0.72, and a likelihood ratio of 7.9. Mean CD11b⁺MDSC levels increased linearly with higher TNM stage (P<0.01) and were 19.4±5.4 in patients with persistent cancer after surgery compared to 13.2±6.8 in those without evidence of disease (P<0.05). <b>Conclusion:</b> MDSC measurement using this flow-cytometry based assay represents a novel approach for pre-operatively assessing malignancy risk and cancer extent in patients with thyroid nodules. While further validation is needed, MDSC assessment may serve as a useful adjunct when cytology is indeterminate, and predict tumor stage and recurrence risk in cases of thyroid cancer.

PMID: 26756227 [PubMed - as supplied by publisher]

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