BRAF V600E and Retinoic Acid in Radioiodine-Refractory Papillary Thyroid Cancer

Jan Benedikt Groener; Debora Gelen; Carolin Mogler; Esther Herpel; Csaba Toth; Zoltan Kender; Marco Peichl; Sabine Haufe; Uwe Haberkorn; Alba Sulaj; Johanna Zemva; Stefan Kopf; Peter Paul Nawroth; Maik Brune; Gottfried Rudofsky

doi:10.1055/a-0765-9078

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2019; 51(01): 69-75
DOI: 10.1055/a-0765-9078

Endocrine Care

BRAF V600E and Retinoic Acid in Radioiodine-Refractory Papillary Thyroid Cancer

Jan Benedikt Groener

¹Department of Endocrinology and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

,

Debora Gelen

¹Department of Endocrinology and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

,

Carolin Mogler

²Department of Pathology, Technical University of Munich, Munich, Germany

,

Esther Herpel

³Tissue Bank of the National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany

⁴Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany

,

Csaba Toth

³Tissue Bank of the National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany

⁴Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany

,

Zoltan Kender

¹Department of Endocrinology and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

,

Marco Peichl

⁵Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany

,

Sabine Haufe

⁵Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany

,

Uwe Haberkorn

⁵Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany

⁶Clinical Cooperation Unit Nuclear Medicine, Deutsches Krebsforschungszentrum, Heidelberg, Germany

,

Alba Sulaj

¹Department of Endocrinology and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

,

Johanna Zemva

¹Department of Endocrinology and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

,

Stefan Kopf

¹Department of Endocrinology and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

,

Peter Paul Nawroth

¹Department of Endocrinology and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

,

Maik Brune

¹Department of Endocrinology and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

,

Gottfried Rudofsky

¹Department of Endocrinology and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

⁷Department of Endocrinology, Cantonal Hospital Olten, Olten, Switzerland

› Author Affiliations

Abstract

Radioiodine refractoriness in differentiated thyroid cancer remains an unsolved therapeutic problem. Response to retinoids might depend on specific genetic markers. In this retrospective analysis, associations between BRAF V600E and clinical outcomes after redifferentiation with retinoic acid (RA) and radioiodine therapy (RIT) were investigated. Thirteen patients with radioiodine-refractory (RAI-R) papillary thyroid cancer (PTC) were treated with 13-cis-RA followed by iodine-131 treatment at the Department of Endocrinology, Heidelberg University Hospital, Heidelberg, Germany. DNA sequencing was performed in formalin-fixed paraffin-embedded tissue. Clinical outcome parameters were tumor size, thyroglobulin, and radioiodine uptake in correlation to mutational status. Differences of each parameter were compared before and after RA/RIT. Initial response showed no difference in patients with BRAF V600E compared to patients with wild type. However, after a median follow-up of 2 and a half years, 2 out of 3 patients with BRAF V600E showed response compared to 5 out of 9 with wild type under consideration of all 3 parameters. In this small cohort, more RAI-R PTC patients with BRAF V600E receiving redifferentiation therapy showed response. Verification in a larger study population analyzing mutational status in patients with RAI-R PTC might be helpful to identify patients where redifferentiation therapy might lead to an improved outcome.

Key words

differentiated thyroid cancer - radioiodine therapy - retinoic acid - genetic markers

Full Text

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