Diagnostic value of AHNAK2 immunohistochemical expression in papillary thyroid carcinoma: an immunohistochemical study

Multiple immunohistochemical markers including galectin-3 and BRAF V600E have been used to identify benign and malignant thyroid tumors. AHNAK nucleoprotein 2 (AHNAK2) is a novel oncogene that belongs to the AHNAK protein family and is upregulated in many malignant tumors, including thyroid cancers. However, its actual value in pathological diagnosis remains unknown. Therefore, we utilized a set of well-studied markers to further confirm the diagnostic role of AHNAK2 in differentiating thyroid tumors. Two hundred ninety-six papillary thyroid carcinomas (PTCs), 167 follicular adenomas (FAs), 36 follicular thyroid carcinomas (FTCs), and 11 non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) were collected. Markers including AHNAK2, galectin-3, BRAF V600E, HBME-1, Thyroid Peroxidase (TPO), CD56, and cyclin-D1 were used simultaneously for immunohistochemistry (IHC). The positivity rates of the PTC markers were as follows: AHNAK2 (95%), galectin-3 (89.5%), BRAF V600E (82.4%), HBME-1 (84.1%) CK19 (99.7%), cyclin-D1 (98.0%), TPO (61.1%), and CD56 (47.3%). AHNAK2 (4.2%), galectin-3 (6.0%), BRAF V600E (0.0%), HBME-1 (16.8%); CK19 (88.6%), cyclin-D1 (78.4%), TPO (94.0%), and CD56 (94.6%) were identified in FA. The areas under the receiver operating characteristic (ROC) curves for each marker in distinguishing PTCs from FAs were AHNAK2 (0.964), galectin-3 (0.935), BRAF V600E (0.907), HBME-1 (0.882), cyclin-D1 (0.776), CK19 (0.752), CD56 (0.053), TPO (0.004), and AHNAK2 in combination with galectin-3 and BRAF V600E (0.992). We firstly found that AHNAK2 was highly expressed in PTC and could be a new promising diagnostic marker for distinguishing thyroid tumors. The combination of AHNAK2 with galectin-3 and BRAF V600E can serve as an efficient diagnostic IHC panel for thyroid cancer, with great clinical potential.