title: 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.
authors.affiliation: Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, AB190.11, 6621 Fannin Street, Houston, TX, 77030, USA, hao.wu@bcm.edu.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Huihui
authors.initials: H
authors.lastname: Ye
authors.forename: Shi
authors.initials: S
authors.lastname: Yang
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Lee
authors.forename: Antonio
authors.initials: A
authors.lastname: de las Morenas
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D065646:Thyroid Carcinoma, Anaplastic / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C117307:KRAS protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)