Diagnosis of post-surgical fine-needle aspiration biopsies of thyroid lesions with indeterminate cytology using HRMAS NMR-based metabolomics
Ultrasound examination coupled with fine-needle aspiration (FNA) cytology is the gold standard for the diagnosis of thyroid cancer. However, about 10–40% of these analyses cannot be conclusive on the malignancy of the lesions and lead to surgery. The cytological indeterminate FNA biopsies are mainly constituted of follicular—patterned lesions, which are benign in 80% of the cases.
The development of a FNAB classification approach based on the metabolic phenotype of the lesions, complementary to cytology and other molecular tests in order to limit the number of patients undergoing unnecessary thyroidectomy.
We explored the potential of a NMR-based metabolomics approach to improve the quality of the diagnosis from FNABs, using thyroid tissues collected post-surgically.
The NMR-detected metabolites were used to produce a robust OPLSDA model to discriminate between benign and malignant tumours. Malignancy was correlated with amino acids such as tyrosine, serine, alanine, leucine and phenylalanine and anti-correlated with myo-inositol, scyllo-inositol and citrate. Diagnosis accuracy was of 84.8% when only indeterminate lesions were considered.
These results on model FNAB indicate that there is a clear interest in exploring the possibility to export NMR metabolomics to pre-surgical diagnostics.
KeywordsThyroid cancer Fine-needle aspiration Indeterminate cytology Follicular NMR-based metabolomics Diagnosis
Fine-needle aspiration biopsy
Follicular thyroid carcinoma
Papillary thyroid carcinoma
Medullary thyroid carcinoma
Tll cell variant of papillary thyroid carcinoma
Classic variant of papillary thyroid carcinoma
Follicular variant of papillary thyroid carcinoma
High-resolution magic angle spinning
Nuclear magnetic resonance
Principal component analysis
Orthogonalized projections to the latent structures discriminant analysis
Cross-validation analysis of variance
Variable importance in the prediction
This study was funded by Agence nationale de la recherche (Grant No. ANR-2011- JS08-014-01).
PM, FB and SC designed research. LR, AS performed research. AS and LT performed the cytological and histological analyses. LS analysed the data. LS and LT wrote the paper. All authors read and approved the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments and approved by the Local Ethics Committee of the Azienda Ospedaliero Universitaria Pisana.
Informed consent was obtained from all individual participants included in the study.
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