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The prevalence of thyroid carcinoma is increasing and represents the most common endocrine malignancy, with papillary thyroid carcinoma (PTC) being the most frequent subtype. The genetic alterations identified in PTCs fail to distinguish tumors with different clinical behaviors, such as extra-thyroidal extension and lymph node metastasis. We hypothesize that the immune microenvironment may play a critical role in tumor invasion and metastasis. Computational immunogenomic analysis was performed on 568 PTC samples in The Cancer Genome Atlas using both CIBERSORT and TIMER deconvolution analytic tools for characterizing immune cell composition. Immune cell infiltrates were correlated with histologic type, mutational type, tumor pathologic T stage, and lymph node N stage. Dendritic cells (DCs) are highly associated with more locally advanced tumor T stage [T3/T4, Odds Ratio (OR)=2.6, Confidence Interval (CI)=1.4-4.5, p=5.4 x 10-4]. Increased dendritic cells (OR=3.4, CI=1.9-6.3, p=5.5 x 10-5) and neutrophils (OR=10.5, CI=2.7-44, p=8.7 x 10-4) significantly correlate with lymph node metastasis. In addition, dendritic cells positively correlate with tall cell morphology (OR=4.5, CI=1.6-13, p=4.9 x10-3) and neutrophils negatively correlate with follicular morphology (OR=1.3 x 10-3, CI=5.3 x 10-5-0.031, p=4.1 x 10-5). TIDE analysis indicates an immune-exclusive phenotype that may be mediated by increased galectin-3 found in PTCs. Thus, characterization of the PTC immune microenvironment using two computational platforms shows that specific immune cells correlate with mutational type, histologic type, local tumor extent, and lymph node metastasis. Immunologic evaluation of PTCs may provide a better indication of biologic behavior, resulting in the improved diagnosis and treatment of thyroid cancer.
This article was published in the following journal.
Name: Endocrine-related cancer
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A group of carcinomas which share a characteristic morphology, often being composed of clusters and trabecular sheets of round "blue cells", granular chromatin, and an attenuated rim of poorly demarcated cytoplasm. Neuroendocrine tumors include carcinoids, small ("oat") cell carcinomas, medullary carcinoma of the thyroid, Merkel cell tumor, cutaneous neuroendocrine carcinoma, pancreatic islet cell tumors, and pheochromocytoma. Neurosecretory granules are found within the tumor cells. (Segen, Dictionary of Modern Medicine, 1992)
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