Possibilities of immunocytochemical staining for HBME-1 expression in the «diagnostic search» of differentiated thyroid cancer. Own investigation

Abstract

Objective — to investigate HBME-1 expression variants on cytological material classified as doubtful (III, IV, V), according to the Bethesda categories, to evaluate the value of the HBME-1 expression test on the corresponding histological material of nodular goiter, follicular tumor with an uncertain potential for malignancy for the differential diagnosis of thyroid carcinoma (ThC). Materials and methods. The analysis was performed on the data of 14 patients with thyroid nodular lesions and cytological Bethesda categories III, IV, and V (“gray zone“). The HBME-1 expression was determined by the results of immunocytochemical (ICC) and immunohistochemical (IHC) staining with the use of mouse monoclonal antibodies against human HBME-1 (1 : 500; cat № BSB 3459; «Bio SB» «Bioscince for the World» Santa Barbara USA). The HBME-1 expression grade was calculated as the sum of the score for staining intensity and cytoplasmic positive cells square, present in the IHC sample. HBME-1 positive result was considered with an IHC score >6 point. Results. From 14 investigated patients, five were defined as HBME-1 positive. According to the postoperative histological conclusion for the group of HBME-1 positive patients, thyroid carcinoma was diagnosed in four subjects, including three cases of papillary ThC and one follicular ThC; in one patient follicular tumor of uncertain malignant potential (FT-UMP) was reported. Importantly, immunocytochemical and immunohistochemical HBME-1 reactions in the specimens of these patients were of the same intensity. Among 9 HBME-1 preoperative negative patients, none had malignancy according to the final histological study. Nodular goiter was diagnosed in six patients, and tumor of uncertain malignant potential (FT-UMP) was reported for three subjects. Histological specimens of all 9 patients were HBME-1 negative as well. The obtained results demonstrated an increase in cancer detection rates with increasing Bethesda category. Application of statistical software for biomedical research МedCalc revealed that positive predictive value (PPV) of the HBME-1 expression test was 80% (95% confidence interval CI 38.4—96.3%), and diagnostic efficiency was 92.9% (CI 66.1—99.8%). These results suggest the great potential of the test, however, due to the limited observations, the confidence intervals are too wide. Conclusions. HBME-1 can be used as an immuno­cytochemical marker for the differentiation of benign and malignant thyroid nodules, its use will help to reduce the number of unnecessary surgical removals of benign tumors, which will improve the quality of life of patients and reduce the burden on medical services.