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.
MeSH Terms
Adenocarcinoma, Follicular/genetics,metabolism,mortality,secondary
Adult
Aged
B7-H1 Antigen/metabolism
Biomarkers, Tumor/genetics,metabolism
ErbB Receptors/genetics
Female
Follow-Up Studies
Humans
Male
Middle Aged
Mutation/genetics
Neoplasm Metastasis
Neoplasm Staging
Prognosis
Proto-Oncogene Proteins B-raf/genetics
Proto-Oncogene Proteins c-kit/metabolism
Proto-Oncogene Proteins p21(ras)/genetics
Retrospective Studies
Survival Rate
Thyroid Carcinoma, Anaplastic/genetics,metabolism,mortality,pathology
Thyroid Neoplasms/genetics,metabolism,mortality,pathology
Chemicals
B7-H1 Antigen
Biomarkers, Tumor
CD274 protein, human
KRAS protein, human
EGFR protein, human
ErbB Receptors
Proto-Oncogene Proteins c-kit
BRAF protein, human
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins p21(ras)
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wu Hao
Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, AB190.11, 6621 Fannin Street, Houston, TX, 77030, USA, hao.wu@bcm.edu.
Sun Yue
Ye Huihui
Yang Shi
Lee Stephanie L
de las Morenas Antonio
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