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Genetic profiling of advanced radioactive iodine-resistant differentiated thyroid cancer and correlation with

Rebecca B Schechter1, Madhavi Nagilla1, Loren Joseph2

  • 1Department of Medicine, University of Chicago, Chicago, IL, USA.

Cancer Letters
|February 3, 2015
PubMed

Insights

Molecular markers in differentiated thyroid cancer (DTC) did not predict response to axitinib treatment. Further research is needed to explore VEGFR alterations in DTC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Biomarkers for predicting response to multi-kinase inhibitors in advanced radioiodine-resistant differentiated thyroid cancer (DTC) are lacking.
  • Axitinib is a multi-kinase inhibitor used in treating advanced DTC.
  • Understanding molecular alterations in DTC is crucial for personalized treatment strategies.

Purpose of the Study:

  • To identify molecular markers in DTC that correlate with clinical outcomes in patients treated with axitinib.
  • To investigate the relationship between specific genetic mutations, copy number variations, and protein expression with treatment response.

Main Methods:

  • Genomic DNA was isolated from pretreatment DTC tumor blocks of 18 patients treated with axitinib.
  • OncoCarta™ Mutation Panel was used to screen for 238 oncogenic mutations.
  • Quantitative PCR (qPCR) assessed copy numbers of VEGFR1-3 and PIK3CA.
  • VEGFR sequencing and immunohistochemistry evaluated protein expressions of VEGFRs, c-Met, and PIK3CA.

Main Results:

  • BRAF V600E mutations were found in 22% of tumors, KRAS in 11%, and HRAS in 11%.
  • Increased copy numbers of PIK3CA (33%), VEGFR2 (22%), and VEGFR3 (33%) were observed.
  • No significant correlation was found between molecular alterations and clinical response (best response or progression-free survival).

Conclusions:

  • Molecular evaluation of DTC specimens did not predict clinical response to axitinib in this study.
  • The study identified molecular changes in VEGFR that warrant further investigation.
  • Differentiated thyroid cancer exhibits genetic heterogeneity, with primary and metastatic lesions showing concordant alterations in some cases.
Keywords:
Advanced differentiated thyroid cancerAxitinibBRAFPIK3CARASVEGFR

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