The incidence of thyroid cancer has more than doubled in the last 30 years with nearly 50% of this increase attributable to papillary microcarcinomas (PMC). Despite compeling evidence that cautious observation is a safe and effective alternative to immediate surgical resection, very few PMC patients in the United States are given the option of an active surveillance approach. This is in part due to reports in the literature of a small percentage of patients with PMC that develop loco-regional or distant metastases. Unfortunately, neither clinical features, nor the mutational status ofthe known thyroid cancer oncogenes reliably identify the few PMC patients destined to develop clinically significant disease progression. Since only a small minority of PMC progress to clinically significant disease, it is imperative that we critically re-evaluate the current management paradigm that indiscriminately recommends immediate surgical intervention without giving patients an option for active surveillance. We propose to use both paraffin embedded tissue samples from our pathology archives and fresh frozen PMC samples obtained after 2-5 years of observation in a prospective active surveillance trial to identify molecular events that are predictive of disease progression through a comprehensive evaluation of the PMC cancer genome using massively parallel next generation exon sequencing of 230 genes commonly mutated in cancer coupled to quantitative expression profiling using a custom-designed NanoString platform. Our goal is to identify genomic predictors of disease progression in PMC so that tumors likely to develop into clinically significant disease can be surgically removed, whereas the vast majority that are unlikely to grow or metastasize can be followed with periodic surveillance.
Aim 1 : To perform indepth genomic profiling of PMCs without metastatic disease compared to PMCs with loco-regional and/or distant metastasis.
Aim 2 : To identify genomic predictors of disease progression in a prospectively followed population of patients with PMC.

Public Health Relevance

Even though most patients with papillary microcarcinoma (PMC) do not require immediate surgery, very few are given the option of active surveillance. Our goal is to identify molecular predictors of disease progression that can be used to differentiate the PMC patients that may benefit from an early surgical intervention from the remaining majority that can be followed with observation.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Sloan-Kettering Institute for Cancer Research
New York
United States
Zip Code
Ibrahimpasic, Tihana; Xu, Bin; Landa, IƱigo et al. (2017) Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification of MED12 and RBM10 as Novel Thyroid Cancer Genes Associated with Tumor Virulence. Clin Cancer Res 23:5970-5980
Orlacchio, Arturo; Ranieri, Michela; Brave, Martina et al. (2017) SGK1 Is a Critical Component of an AKT-Independent Pathway Essential for PI3K-Mediated Tumor Development and Maintenance. Cancer Res 77:6914-6926
Montero-Conde, Cristina; Leandro-Garcia, Luis J; Chen, Xu et al. (2017) Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene. Proc Natl Acad Sci U S A 114:E4951-E4960
Park, Spencer; Shevlin, Enda; Vedvyas, Yogindra et al. (2017) Micromolar affinity CAR T cells to ICAM-1 achieves rapid tumor elimination while avoiding systemic toxicity. Sci Rep 7:14366
Min, Irene M; Shevlin, Enda; Vedvyas, Yogindra et al. (2017) CAR T Therapy Targeting ICAM-1 Eliminates Advanced Human Thyroid Tumors. Clin Cancer Res 23:7569-7583
Sherman, Eric J; Dunn, Lara A; Ho, Alan L et al. (2017) Phase 2 study evaluating the combination of sorafenib and temsirolimus in the treatment of radioactive iodine-refractory thyroid cancer. Cancer 123:4114-4121
Di Cristofano, Antonio (2017) SGK1: The Dark Side of PI3K Signaling. Curr Top Dev Biol 123:49-71
Anelli, Viviana; Villefranc, Jacques A; Chhangawala, Sagar et al. (2017) Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression. Elife 6:
Brito, Juan P; Ito, Yasuhiro; Miyauchi, Akira et al. (2016) A Clinical Framework to Facilitate Risk Stratification When Considering an Active Surveillance Alternative to Immediate Biopsy and Surgery in Papillary Microcarcinoma. Thyroid 26:144-9
Mandal, Rajarsi; Chan, Timothy A (2016) Personalized Oncology Meets Immunology: The Path toward Precision Immunotherapy. Cancer Discov 6:703-13

Showing the most recent 10 out of 29 publications