Immunohistochemical markers in diagnosis of papillary thyroid carcinoma: utility of HBME1 combined with CK19 immunostaining

Abstract

Papillary thyroid carcinoma and its variants can be difficult to distinguish from cellular adenomatous nodules. Prior studies have advocated various antibodies to aid in the differential diagnosis, but there is little agreement on their utility. We undertook this study to evaluate immunohistochemical markers in the diagnosis and differential diagnosis of papillary thyroid carcinoma. Ten cases of papillary thyroid carcinoma were initially stained for HBME1, CK19, fibronectin1, Ki-67, Calretinin, p16, SFTPB and CITED1. Additionally, two previously untested antibodies to molecules that have been found to be upregulated in papillary thyroid carcinoma (CST6 and EPS8) were also evaluated. Of these, only HBME1, CK19 and fibronectin1 showed diagnostic utility. These three markers were then further evaluated in 51 papillary thyroid carcinomas and 57 benign thyroids. HBME1 was the most sensitive and specific marker, staining 49/51 papillary thyroid carcinomas and only 4/57 benign thyroids. CK19 was equally sensitive staining all 51 papillary thyroid carcinomas, but it was nonspecific staining 39 of 57 benign thyroids. A negative result, however, was helpful in excluding papillary thyroid carcinoma. Fibronectin1 was positive in 35/51 papillary thyroid carcinomas (69%) and 4/57 (7%) benign thyroids, but its utility was hampered by high background staining. These findings suggest that the combination of HBME1 and CK19 has the greatest diagnostic utility in the differentiation of papillary thyroid carcinoma from its benign mimics.

Paired box gene 8, HBME‐1, and cytokeratin 19 expression in preoperative fine‐needle aspiration of papillary thyroid carcinoma

“…12,13 In the same study, it was deemed nonspecific because it also stained 68.4% of BTN cases, findings confirmed by other authors. 13,18 Although CK19 may focally stain benign lesions, diffuse and strong staining is considered typical of PTC, with a proposed cutoff value of !10% immunoreactive cells to differentiate carcinomas from adenomas. 11,16,17 The combination of HBME-1 and CK19 has been proposed to demonstrate the highest diagnostic value for the differential diagnosis of PTC, with specificity values for the diagnosis of PTC of up to 100% when coexpression of HBME-1 and CK19 is demonstrated.…”

“…10,11 Its utility in thyroid carcinomas has been documented in several studies, revealing strong and diffuse cytoplasmic staining in PTCs. [12][13][14][15][16][17] It is considered the most specific marker (96%) for PTC by some authors, and the most sensitive and specific marker by others, reportedly staining 96% of PTCs and only 7% of BTN cases. 12,13 Other studies have demonstrated that immunoreactivity for HBME-1 is an indication of thyroid malignancy, but not necessarily of papillary differentiation.…”

“…[12][13][14][15][16][17] It is considered the most specific marker (96%) for PTC by some authors, and the most sensitive and specific marker by others, reportedly staining 96% of PTCs and only 7% of BTN cases. 12,13 Other studies have demonstrated that immunoreactivity for HBME-1 is an indication of thyroid malignancy, but not necessarily of papillary differentiation. 11,16,17 Caution is warranted in the interpretation of positive HBME-1 staining in thyroid lesions considered in the differential diagnosis of PTC because HBME-1 staining has also been observed focally in Hashimoto thyroiditis, in which some cells may even demonstrate nuclear changes similar to those of PTC.…”

“…11,16,17 Caution is warranted in the interpretation of positive HBME-1 staining in thyroid lesions considered in the differential diagnosis of PTC because HBME-1 staining has also been observed focally in Hashimoto thyroiditis, in which some cells may even demonstrate nuclear changes similar to those of PTC. 13 For some authors, CK19 is considered the most sensitive marker for PTC, and a negative CK19 result has even been proposed to rule out PTC because it was reported to have stained 100% of the PTC cases studied. 12,13 In the same study, it was deemed nonspecific because it also stained 68.4% of BTN cases, findings confirmed by other authors.…”

“…13 For some authors, CK19 is considered the most sensitive marker for PTC, and a negative CK19 result has even been proposed to rule out PTC because it was reported to have stained 100% of the PTC cases studied. 12,13 In the same study, it was deemed nonspecific because it also stained 68.4% of BTN cases, findings confirmed by other authors. 13,18 Although CK19 may focally stain benign lesions, diffuse and strong staining is considered typical of PTC, with a proposed cutoff value of !10% immunoreactive cells to differentiate carcinomas from adenomas.…”