PAPPA Expression in Indeterminate Thyroid Nodules as Screening Test to Select Patients for Molecular Testing

Area of Science:

• Oncology
• Biochemistry
• Molecular Diagnostics

Background:

• Pregnancy-associated plasma protein A (PAPPA) is implicated as an oncogene with elevated expression in various cancers, including thyroid cancer.
• Molecular testing aids in managing indeterminate thyroid nodules but faces accessibility and cost challenges.
• Current diagnostic pathways for indeterminate thyroid nodules can be resource-intensive.

Purpose of the Study:

• To investigate the potential of PAPPA expression as a novel screening biomarker for indeterminate thyroid nodules.
• To evaluate the utility of PAPPA as a cost-effective adjunct to molecular testing in thyroid nodule evaluation.
• To determine if PAPPA expression levels correlate with malignancy in thyroid nodules.

Main Methods:

• Analysis of PAPPA expression in 107 fine needle aspiration cytologies (FNAC) from Bethesda III-IV indeterminate thyroid nodules.
• Comparison of PAPPA expression levels in samples with and without known mutations.
• Assessment of diagnostic performance metrics including sensitivity and negative predictive value.

Main Results:

• PAPPA expression was significantly elevated in indeterminate thyroid cytological samples.
• Elevated PAPPA expression demonstrated high sensitivity (97.14%) and negative predictive value (98%) for identifying nodules requiring further molecular testing.
• The increased PAPPA expression was not associated with specific oncogenic mutations.

Conclusions:

• PAPPA expression serves as a promising biomarker for screening indeterminate thyroid nodules.
• Assessing PAPPA levels can help identify patients who would benefit most from molecular testing, potentially reducing healthcare costs.
• This approach offers a valuable tool for optimizing the diagnostic workup of thyroid nodules.