Stratifying the risk of malignancy in indeterminate thyroid nodules

Description:

Project ID D2019-45

Background
Thyroid cancer is the most common endocrine cancer globally, and accounts for 3.4% of all new cancer cases in the US. Although several clinical guidelines to detect/manage thyroid nodules are available, a great deal of controversy still exists around the optimal approach for diagnosis. Approximately 20-30% of cytology results from thyroid fine-needle aspiration (FNA) fall into one of three indeterminate diagnostic categories. In recent years, a number of molecular and gene mutation diagnostic tests have been developed to diagnose the indeterminate thyroid nodules in FNA specimens. However, nearly half of patients recommended for surgery based on these tests are still found to have a benign nodule. Therefore, there is a need for a more accurate predictive and prognostic test for thyroid cancer.

Description
Researchers at the University of Toledo have found that thyroid nodule microenvironment cell-profiling analysis can be used as a diagnostic and prognostic marker for thyroid cancer. This approach uniquely focuses on the phenotype, rather than the genotype, of the tumor microenvironment.

Recently described Double Negative (DN) T-cells were significantly more abundant in lymphocytic infiltrates of thyroid cancer. They were shown to downregulate proliferation and cytokine production of cytotoxic T cells present in the tumor microenvironment and contribute to tumor tolerance and active avoidance of tumor immunity. If the quantity of DN T cells exceeds a defined threshold, it indicates a higher likelihood of the presence of cancer.  Aside from immune cell profiling flowcytometric analysis, this approach integrates information derived from transcriptome/meta-analysis of the genome and cytokine/chemokine signal analysis all from the tumor microenvironment of thyroid FNAs. 

Application 

  • Diagnosis of thyroid cancer from FNA samples
  • Predictive tool of severity of disease

Advantages

  • Microenvironment profiling can provide a unique way to diagnose and assess disease severity/progression
  • Sheds light on cellular cross-talk; more accurate diagnosing and preventing unnecessary surgeries

IP Status:                           Patent Pending

Publications:                     1. Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity. Endocr Relat Cancer. 2014 Jun;21(3):505-16

                                       2. Nature of coexisting thyroid autoimmune disease determines success or failure of tumor immunity in thyroid cancer. J Immunother Cancer. 2019 Jan 7;7(1):3

 3. Incidentally discovered papillary thyroid microcarcinomas are more frequently found in patients with chronic lymphocytic thyroiditis than with multinodular goiter or Graves disease. Thyroid. 2020 Apr;30(4):531-535

 4. Higher TSH Is Not Associated With Thyroid Cancer Risk in the Presence of Thyroid Autoimmunity.  J Clin Endocrinol Metab. 2020 Jul 1;105(7)

Patent Information:
Category(s):
Diagnostics
Oncology
For Information, Contact:
Katherine Pollard
Licensing Associate
The University of Toledo
419-530-6228
katherine.pollard@utoledo.edu
Inventors:
Shahnawaz Imam
Juan Jaume
Keywords:
Atypia of undetermined significance (AUS)
Euthyroid Hashimoto thyroiditis (EHT)
Fine needle aspiration (FNA)
Follicular lesion of undetermined significance (FLUS)
Thyroid
Thyroid cancer diagnostic/prognostic markers