Anaplastic Thyroid Cancer: Outcome and the Mutation/Expression Profiles of Potential Targets

Abstract

Anaplastic thyroid cancer (ATC) is a rare but aggressive malignancy of the thyroid. No effective treatment modalities are currently available. Targeted therapy against protein kinases showed promising results in preclinical studies. Our goal was to assess the mutational status of potential therapeutic targets, as well as the biomarker for immunotherapy in the clinical context. Using allele specific PCR, Sanger sequencing, fragment analysis and immunohistochemistry, we assessed BRAF, KRAS, EGFR mutations and protein overexpression of C-KIT and PDL1 in anaplastic thyroid cancer specimens. Results were compared to clinical information and patient outcome to assess the utility of these biomarkers. There were 13 patients in our study with a median overall survival of 19 weeks. Of the 13 ATC patients, 3 (23 %) had BRAF V600E mutation. C-KIT overexpression was found in 1 (8 %) patient who responded well to a tyrosine kinase inhibitor. PDL1 expression was seen in 3 (23 %) patients, none of them were surgical candidates due to unresectability and poor performance status. KRAS codon 12/13 and EGFR exon 18, 19, 20 and 21 were all wild type in our patients. Protein kinase inhibitors and immunotherapy may be useful adjuvant therapies for ATC.

Programmed death-ligand 1 overexpression is a prognostic marker for aggressive papillary thyroid cancer and its variants

“…Several other cancers have been reported to have increased PD-L1 expression in the plasma membrane alone or in both plasma membrane and cytoplasm [22–25]. The PD-L1 antibody used in this study is a well-established one and had been used for immunohistochemical analysis in different types of cancers by several other groups [26–31].…”

Very low expression of PD-L1 in medullary thyroid carcinoma

“…Regarding thyroid tumors, a few papers have reported on PD-L1 expression in thyroid (Cunha et al 2013, Angell et al 2014, Wu et al 2015, Bastman et al 2016, Chowdhury et al 2016, Ahn et al 2017, Shi et al 2017). With the exception of two studies on anaplastic (undifferentiated) thyroid carcinoma (ATC) (Wu et al .…”

SPC24 is critical for anaplastic thyroid cancer progression

“…Although ATC is rare, it is one of the most aggressive human cancers and the average survival time of ATC is only 6 to 8 months and the 5-year survival rate of ATC is only 0 ∼ 10% [3, 4]. Most patients die due to tumor invasion or distant metastases.…”