- Project 4 Project 4 is a new project that addresses the epidemic of thyroid cancer. Well-differentiated thyroid cancer is increasing at an alarming rate. There has been a 3-fold increase in incidence of thyroid cancer in the past 3 decades. However, the mortality for these patients has remained very low (estimated to be ~2%). Therefore, performing a thyroidectomy for all patients with that thyroid cancer may not be necessary. This project addresses two major issues relevant to the thyroid cancer detection and management. Firstly, we will use next generation sequencing to develop and validate a molecular test that can more accurately distinguish between thyroid cancer and benign nodules in patients with needle biopsy results that are indeterminate. This molecular test analyses the expression and/or mutation of 62 individual genes and builds on our previous experience using a smaller panel of genes to diagnose thyroid cancer. In the second Aim, we will evaluate the ability of our molecular testing to differentiate low-risk thyroid cancers from more aggressive (high-risk) thyroid cancers. In order to accomplish this goal, we will first interrogate tissue samples obtained from patients who have undergone surgery for thyroid cancer, and then experience disease recurrence or distant metastases. Simultaneously, we will initiate a clinical trial to observe patients with small thyroid cancers. Patients with small cancers will undergo upfront molecular testing and then will be observed. A molecular profile of high-risk disease will be determined by the tumors from patients who progress during the observation period. This information will then be used to inform the second phase of the trial, which will use the molecular signature to separate patients into high-risk and low-risk disease for surgery or observation, respectively.
Aim 1 : To test the hypothesis that the NGS-based panel of mutational markers can reliably diagnose cancer in thyroid nodules.
This Aim seeks to develop and validate a novel molecular analytic test that can accurately predict which thyroid nodules are malignant versus benign. We will develop the molecular test at the University of Pittsburgh and then validate the utility of this test in 8 other academic centers.
Aim 2 : To test the hypothesis that high-risk and low-risk differentiated thyroid cancers have distinct mutational profiles that can be detected in FNA samples and utilized to guide patient management.
This Aim consists of two parts, the first sub-aim seeks to use molecular testing to characterize tissues derived from patients with aggressive disease (experience recurrence of cancer or develop metastases). The second sub- aim extends these data to develop and implement a prospective clinical trial that provides patients with small cancers to have observation instead of surgery. The data from this trial will validate that molecular testing can be used to stratify thyroid cancers into a low-risk subtype.

Public Health Relevance

- Project 4 Well-differentiated thyroid cancer (mostly papillary thyroid cancer) is largely an indolent disease. Thyroid surgery may not be necessary in many patients who currently undergo invasive procedures for diagnosis and/or treatment. This research builds on a track record at the University of Pittsburgh of developing, and translating into clinical practice, molecular testing for thyroid disease. At the conclusion of this study, we expect to use molecular testing to accurately predict those patients who can safely avoid thyroid surgery.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
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Special Emphasis Panel (ZCA1)
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Hubbard, Leah
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University of Pittsburgh
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Johnston, Paul A; Sen, Malabika; Hua, Yun et al. (2018) High Content Imaging Assays for IL-6-Induced STAT3 Pathway Activation in Head and Neck Cancer Cell Lines. Methods Mol Biol 1683:229-244
Palliyaguru, Dushani L; Yuan, Jian-Min; Kensler, Thomas W et al. (2018) Isothiocyanates: Translating the Power of Plants to People. Mol Nutr Food Res 62:e1700965
Gleber-Netto, Frederico O; Zhao, Mei; Trivedi, Sanchit et al. (2018) Distinct pattern of TP53 mutations in human immunodeficiency virus-related head and neck squamous cell carcinoma. Cancer 124:84-94
Santuray, Rodell T; Johnson, Daniel E; Grandis, Jennifer R (2018) New Therapies in Head and Neck Cancer. Trends Cancer 4:385-396
Liu, Zhuqing; McMichael, Elizabeth L; Shayan, Gulidanna et al. (2018) Novel Effector Phenotype of Tim-3+ Regulatory T Cells Leads to Enhanced Suppressive Function in Head and Neck Cancer Patients. Clin Cancer Res 24:4529-4538
Lu, Shanhong; Concha-Benavente, Fernando; Shayan, Gulidanna et al. (2018) STING activation enhances cetuximab-mediated NK cell activation and DC maturation and correlates with HPV+ status in head and neck cancer. Oral Oncol 78:186-193
Nikiforova, Marina N; Mercurio, Stephanie; Wald, Abigail I et al. (2018) Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules. Cancer 124:1682-1690
Zhong, Qian; Liu, Zhi-Hua; Lin, Zhi-Rui et al. (2018) The RARS-MAD1L1 Fusion Gene Induces Cancer Stem Cell-like Properties and Therapeutic Resistance in Nasopharyngeal Carcinoma. Clin Cancer Res 24:659-673
Ma, Jing; Salamoun, Joseph; Wipf, Peter et al. (2018) Combination of a thioxodihydroquinazolinone with cisplatin eliminates ovarian cancer stem cell-like cells (CSC-LCs) and shows preclinical potential. Oncotarget 9:6042-6054
Hartman, Douglas J; Ahmad, Fahad; Ferris, Robert L et al. (2018) Utility of CD8 score by automated quantitative image analysis in head and neck squamous cell carcinoma. Oral Oncol 86:278-287

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