MOLECULAR PROFILE AND CLINICAL OUTCOMES IN DIFFERENTIATED THYROID CANCER PATIENTS PRESENTING WITH BONE METASTASIS

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Differentiated thyroid cancer (DTC) rarely presents initially with bone metastasis.
• The molecular characteristics of DTC with bone metastasis are not well understood.
• Understanding these profiles is crucial for effective treatment strategies.

Purpose of the Study:

• To investigate the histopathology and molecular profiles of DTC patients with initial bone metastasis.
• To evaluate the response of these tumors to radioactive iodine (RAI) therapy.
• To identify potential molecular markers predicting treatment response.

Main Methods:

• Retrospective chart review of eight patients with symptomatic bone metastasis from unknown primary DTC.
• Histopathologic review of bone and thyroid tumor specimens.
• Targeted next-generation sequencing of 112 thyroid cancer-related genes in bone metastasis samples.

Main Results:

• Histopathology revealed follicular variant papillary carcinoma (7/8) and tall cell variant papillary carcinoma (1/8).
• High prevalence of telomerase reverse transcriptase (TERT) mutations (88%), often co-occurring with RAS GTPase gene (RAS) mutations (50%).
• Tumors with TERT, RAS, or combined mutations showed radioiodine-avidity and responded to RAI, with decreased thyroglobulin (TG) levels.

Conclusions:

• DTC presenting with bone metastasis, regardless of primary tumor size, frequently harbors TERT mutations, often with coexisting RAS mutations.
• This specific molecular signature (TERT and/or RAS mutations) appears to predict a favorable response to radioactive iodine therapy.
• Further research into these molecular profiles can guide personalized treatment approaches for metastatic DTC.