Thyroid nodules are heterogeneous tumors with variable genetic signatures. Thyroid cancers are monoclonal lesions with a defined histomorphology that largely depends on the underlying somatic mutation. While the mutation rate is generally low in differentiated thyroid cancers, poorly differentiated and anaplastic thyroid cancers show a high mutation load. The identification of somatic mutations in fine needle aspirates can be helpful for the differential diagnostics of thyroid nodules; however, a prognostic contribution is less certain. The molecular pathology of thyroid tumors is helpful for the development of targeted therapies and may infer novel immuno-oncological concepts for advanced aggressive thyroid cancers.

There is little consensus on the optimal treatment approach for newly diagnosed patients. The present study aims to provide additional evidence by evaluating a series of patients diagnosed with anaplastic thyroid carcinoma (ATC) and analyzing factors related to increased survival. This was a retrospective cohort report structured according to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guideline. Demographics, chief complaint, history of prior thyroid cancer, stage at presentation, management modalities (surgery, chemotherapy, radiotherapy, or observation), completeness or resection, and survival period since initial diagnosis were reviewed for patients with documentation of histologic ATC diagnosis between 2003 and 2016. The median survival period for 34 patients (11 males, 23 females) was 93.5 days. Patients aged 70 or younger (111 days) tended to survive longer than those older 70 (88 days) (P = .081). Observation, surgery only, radiotherapy only, and chemo-radiotherapy after surgery group showed median survival of 88 days, 49 days (range 14-528), 61.5 days, and 225 days, respectively. There was also no significant difference in survival between the 10 (29.4%) stage IVb (225 days) and 23 (67.7%) IVc (88 days) patients (P = .242). The median survival of the R1 resection group was 514 days while that of the R2 group was 102 days (P = .338). There were no significant difference between patients with the de novo ATC (112 days) and patients with papillary thyroid carcinoma origin ATC (99 days) (P = .297). Results from our series of 34 patients with ATC show that more intense combination of surgery and chemo-radiotherapy tends to secure a longer survival period. Therefore we recommend a multi-modality approach after a comprehensive consultation with the patient.

Anaplastic carcinoma of the thyroid (ATC), also called undifferentiated thyroid cancer, is the least common but most aggressive and deadly thyroid gland malignancy of all thyroid cancers. The aim of this study is to explore essential biomarker and use CRISPR/Cas9 with lentivirus delivery to establish a gene-target therapeutic platform in ATC cells. At the beginning, the gene expression datasets from 1036 cancers from CCLE and 8215 tumors from TCGA were collected and analyzed, showing EGFR is predominantly overexpressed in thyroid cancers than other type of cancers (P = 0.017 in CCLE and P = 0.001 in TCGA). Using CRISPR/Cas9 genomic edit system, ATC cells with EGFR sgRNA lentivirus transfection obtained great disruptions on gene and protein expression, resulting in cell cycle arrest, cell growth inhibition, and most importantly metastasis turn-off ability. In addition, the FDA-approved TKI of afatinib for EGFR targeting also illustrates great anticancer activity on cancer cell death occurrence, cell growth inhibition, and cell cycle arrest in SW579 cells, an EGFR expressing human ATC cell line. Furthermore, off-target effect of using EGFR sgRNAs was measured and found no genomic editing can be detected in off-target candidate gene. To conclude, this study provides potential ATC therapeutic strategies for current and future clinical needs, which may be possible in increasing the survival rate of ATC patients by translational medicine.