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PMID: 25588542 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Anaplastic thyroid cancer: outcome and the mutation/expression profiles of potential targets.

Pathology oncology research : POR ·Vol. 21 ·No. 3 ·2015-07-00 ·Pages 695-701

Wu H, Sun Y, Ye H, Yang S, Lee SL, de las Morenas A

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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Article Info
Journal
Pathology oncology research : POR
Abbr.
Pathol Oncol Res
ISSN
1532-2807
Published
2015-07-00
Epub
2015-00-15
Pages
695-701
Language
English
Region
Switzerland
NLM ID
9706087
Subset
IM
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