Possibilities of immunohistochemical markers HBME-1, TROP-2, Galectin-3 and Ki-67 to optimize the diagnosis of follicular carcinomas

In clinical practice, there is a diagnostic dilemma in the morphological examination in the verification of follicular carcinomas of the thyroid gland (FTC) and follicular adenoma (FA) among patients who were operated on for a nodular goiter with Bethesda III, IV and V cytological findings. Objective — To study the effectiveness of the use of immunohistochemical (IGH) markers HBME‑1, TROP‑2, Galectin‑3 and Ki‑67 in the diagnosis of FA and FTC on the histological material of patients who were operated on for nodular goiter with a cytological conclusion according to the Bethesda classification III, IV and V. Materials and methods. 124 patients operated on for follicular nodular neoplasms with a cytological conclusion according to Bethesda «Gray zone» were studied, as a result of the pathohistological examination, it was established: FTC — 26 (20.97%), FA — 98 (79.03%). IGH was performed using monoclonal antibodies against human HBME‑1, TROP‑2, Galectin‑3 and Ki‑67 («Bio SB», USA). Evaluation criteria were based on the intensity of staining (scale of 0 to 3) Results. TROP‑2 and Ki‑67 markers provide the highest overall diagnostic efficiency due to high specificity (93.9% and 96.9%, respectively). However, their sensitivity is extremely low (11.5% — Ki‑67, 0% — TROP‑2). That is, these tests have practically no diagnostic utility. From the point of view of detecting the disease, the test based on HBME‑1 is the most useful (sensitivity — 88.5%): only 3 cases out of 26 were missed, but it gives a lot of false positives: 74 out of 98. The test based on Galectin‑3 relatively accurately determines the absence of the disease — correctly identified 78 out of 98 such cases (specificity — 79.6%), but at the same time it is practically ineffective in finding the disease — 9 «triggers» out of 26 cases of FTC. If there is a simultaneous absence of the reaction of the HBME‑1 and Galectin‑3 markers, with a probability of approximately 0.9, it can be expected that the patient does not have FTC. On the other hand, with the maximum strength of the reaction, the probability of detecting FTC reaches 0.667. Conclusions. HBME‑1 (sensitivity 88.5%) turned out to be the most significant IGH marker in the differential diagnosis between FA and FTC. Markers TROP‑2 and Ki‑67 on the IGH study were practically not useful in the detection of FTC (sensitivity 0 and 11.5% respectively). The combined use of HBME‑1 and Galectin‑3 markers proved that the absence of an IGH reaction can be interpreted in favor of the presence of FA in the patient, and the simultaneous positive reaction of both markers is a warning regarding the diagnosis of FTC.