Aggressive variants of papillary thyroid cancer (PTC) have been described with increasing frequency and are associated with unfavorable clinical outcomes. They include diffuse sclerosing variant, tall cell variant, columnar cell variant, solid variant, and hobnail variant. These pathological subtypes are considered in the latest American Thyroid Association guidelines as conferring an intermediate risk of recurrence and were associated with metastasis as well as absence of avidity to radioiodine therapy and lower survival rate.
The correct diagnosis of the most aggressive variants of PTC can still represent a diagnostic challenge even for expert pathologists. Despite recent advances in thyroid cancer genomics, limited data exist on genetic landscape of aggressive variants of thyroid cancer.
The overall aim of this project is to define the genetic landscape of aggressive variants of PTCs and identify genetic alterations of potential diagnostic, prognostic, and therapeutic significance. We will perform targeted next-generation sequencing in aggressive variants of PTC patients and will compare them with advanced thyroid cancers, namely i) differentiated thyroid cancer patients presenting with distant metastases, ii) poorly differentiated thyroid cancers (PDTCs) and iii) anaplastic thyroid cancers (ATCs). As further control, a subgroup of well-differentiated PTCs without distant metastases with a minimum follow-up of 5 years will be selected and common or peculiar genetic features associated with different subtypes of thyroid cancer will be defined.
Patients will be selected from the web-based thyroid cancer database of the Italian Thyroid Cancer Observatory (ITCO), which includes prospective and contemporary observational data. Using a prospective dataset, including baseline data and actual outcome of patients, we can estimate the accuracy of the risk stratification and how it may be improved and modified by the availability of a comprehensive molecular profiling.
Aggressive variants of PTC have been described with increasing frequency and are associated with unfavorable clinical outcomes and lower survival rate.
It is important to identify these patients early in the treatment process. However, the correct diagnosis of the most aggressive variants of PTC can still represent a diagnostic challenge even for expert pathologists.
To date, despite notable advances in thyroid cancer genomics, limited data exist on genetic landscape of aggressive variants of thyroid cancer. The knowledge of genetic events associated with these variants has prognostic significance and will assist in the development of the next generation of molecular tools for the diagnosis and treatment.
Using a prospective dataset like that of ITCO, including baseline data and actual outcome of patients three and five years after the initial treatment, we can estimate the accuracy of the risk stratification and how it may be improved and modified by the availability of a comprehensive molecular profiling.
The integration of clinical, pathological, molecular data, along with the final outcomes detected during long-term follow-up will allow a revision of current assessment strategies for prognostication, disease management, and definition of follow-up strategies for these patients.