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

Pregnancy-associated plasma protein A (PAPPA) acts as an oncogene, and its expression is increased in multiple malignancies, including thyroid cancer. Molecular tests represent a useful tool in the management of indeterminate thyroid nodules; however, they are not conducted in all centers, and they contribute to increase the per-patient cost of nodule evaluation. In this study, we examined whether PAPPA expression could represent a promising new screening test in the management of indeterminate thyroid nodules. Toward this aim, PAPPA expression was evaluated in 107 fine needle aspiration cytologies (FNAC) belonging to Bethesda III–IV categories that had been sent to molecular biology to discriminate the nature of the nodules. We found that the PAPPA expression increased and showed an elevated sensitivity (97.14%) and negative predictive value (98%) in indeterminate cytological samples positive for mutations. The enhanced expression was not linked to a specific oncogene. Our findings demonstrated that assessing the PAPPA expression in indeterminate thyroid cytologies could represent a useful screening tool to select all patients that effectively need to be sent to molecular testing, thereby, leading to a potential cost reduction in the management of patients.