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2016 ; 26
(3
): 381-9
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Circulating Myeloid-Derived Suppressor Cells Predict Differentiated Thyroid
Cancer Diagnosis and Extent
#MMPMID26756227
Angell TE
; Lechner MG
; Smith AM
; Martin SE
; Groshen SG
; Maceri DR
; Singer PA
; Epstein AL
Thyroid
2016[Mar]; 26
(3
): 381-9
PMID26756227
show ga
BACKGROUND: Establishing the preoperative 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. The
authors 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. METHODS: A prospective observational pilot study was performed
of patients undergoing thyroidectomy for a solitary thyroid nodule. The presence
of a thyroid nodule >1?cm was confirmed sonographically, and fine-needle
aspiration biopsy performed prior to surgery in all cases. Peripheral blood
collected preoperatively 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. RESULTS: Of 50 patients included in this
study, MDSC measurement was successful in 47 (94%). One patient was found to have
a concurrent cancer, leaving 46 patients for primary analysis. The cytologic
diagnoses were benign in five (10.8%), atypia or follicular lesion of
undetermined significance in five (10.8%), suspicious for follicular neoplasm in
five (10.8%), suspicious for malignant in three (6.5%), and malignant in 28
(60.1%) of the 46 nodules. Final histopathology was benign in 11 (24%) and DTC in
35 (76%), encompassing 34 PTC cases and one follicular thyroid carcinoma. Mean
percentages of CD11b(+)HLA-DR(low)HIF1a(+) MDSC (CD11b(+)MDSC) were 14.0?±?6.2%
and 7.9?±?3.6% in DTC versus benign nodules, respectively (p?0.005). A cutoff
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 with 13.2?±?6.8 in those without evidence of disease (p?0.05).
CONCLUSION: MDSC measurement using this flow cytometry-based assay represents a
novel approach for preoperatively assessing malignancy risk and cancer extent in
patients with thyroid nodules. While further validation is needed, these data
suggest that MDSC assessment may serve as a useful adjunct when cytology is
indeterminate, and predict tumor stage and recurrence risk in cases of thyroid
cancer.