Clinical Validation of a Molecular Signature to Detect Cancer in Thyroid Nodules With Indeterminate Cytology

1. Principal objective: The primary objective of this study is to validate the diagnostic performance of a Dx15 molecular test based on molecular transcriptomic signatures previously identified in distincts cohorts of samples to determine the malignant or benign profile of a thyroid nodule with indeterminate cytological analysis. The target population includes categories III \[Follicular lesion of undetermined significance or Atypia of undetermined significance (FLUS/AUS)\] and IV \[Follicular neoplasm / Suspicious for follicular neoplasm (FN/SFN)\] of the Bethesda classification. The expected target performance of the Dx15 molecular test in this target population is 95% for specificity with a lower limit of the 95% confidence interval of 87%, and 75% for sensitivity. 2. Secondary objectives: * To assess the performance of the Dx15 test in samples collected during the study by fine-needle aspiration (FNA) in each and in all of the indeterminate Bethesda classification categories (categories III, IV and V: suspected malignancy) * To assess the performance of the TI-RADS ultrasonography score for diagnosing thyroid cancer in patients presenting with a thyroid nodule and having available cytological analysis results. * To check the potential of performance of the molecular signature as well as of its combination with other tests by applying it in a blind manner to samples collected from patients presenting with thyroid nodules and whose aspiration biopsy result is benign (Bethesda category II), malignant (Bethesda category VI) or non-diagnostic (Bethesda category I) * To assess the performance of mutation tests (isolated mutations, chromosomal rearrangements) for diagnosing thyroid cancer in patients presenting with a thyroid nodule and with available cytological results. * To estimate the performance of the combination of the Dx15 test result and other diagnostic tools such as mutation tests and/or the TI-RADS score to diagnose thyroid cancer in patients presenting with a thyroid nodule and having an indeterminate cytology result (especially AUS/FLUS and FN/SFN). The combination of Dx15 diagnostic test results with other study parameters will also be considered in order to establish the option of an algorithmic approach for the diagnosis of thyroid cancer. * To compare the results of cytological and histological analyses obtained in the centres and by centralised reading and assessment of the impact of its results on the other study analyses and parameters. * Additional analyses deemed relevant on the basis of various parameters and data collected during the study. 3. Objective of exploratory research: * The use of all or part of the FNA samples for the purpose of research as part of thyroid cancers, especially with the objective of optimising or identifying additional molecular signatures.

Sex

All

Minimum age

18 Years

1. Patient selection criteria:

   * Men or women aged 18 years or older,
   * Patient presenting with at least one thyroid nodule for which a fine needle aspiration biopsy is indicated for the diagnosis of thyroid cancer,
   * Patient covered by a social security program or benefiting from a comparable program,
   * Patient having signed a written informed consent form to participate in the study. N.B.: the patient must also have signed a specific form for mutation analyses.
2. Patient inclusion criteria:

   * Selection criteria,
   * Patient having undergone a fine-needle aspiration biopsy of a thyroid nodule, the cytological results of which should be classified according to the Bethesda criteria,
   * Patient whose surgical specimen is likely to have undergone histological analysis (benign/malignant) or at least a follow-up and monitoring program allowing diagnosis.
3. Non-inclusion criteria:

   * Adults over 18 years of age who are under legal protection or are unable to give their consent,
   * Patient taking part in another clinical trial likely to affect thyroid function, in the previous month or during the screening process,
   * Patients currently receiving treatment for cancer or in remission for less than two years (except basal or squamous cell skin cancers),
   * Patient presenting with multinodular goitre with no dominant module, i.e. a nodule easily identifiable on imaging and which can monitored throughout the study,
   * Patient not likely to comply with the protocol and, in particular, not to be followed up by the investigating centre throughout the study,
   * Clinically significant, acute and/or unstable disease, which, in the investigator's opinion, is likely to interfere significantly with patient evaluations and follow-up during the study.