SATB2 is an Emergent Biomarker of Anaplastic Thyroid Carcinoma: A Series with Comprehensive Biomarker and Molecular Studies

Abstract

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive thyroid malignancy typically comprised of undifferentiated tumor cells with various histologic morphologies, which makes the diagnosis challenging. These tumors commonly show loss of thyroglobulin and TTF1 with preservation of cytokeratin (67%) and Paired Box Gene 8 (PAX8) (55%) expression. Identification of a sensitive immunohistochemical stain to aid in the diagnosis of ATC would be beneficial. Immunohistochemistry (IHC) against special AT-rich sequence-binding protein 2 (SATB2) protein is a sensitive and specific marker expressed in colorectal adenocarcinoma and bone or soft tissue tumors with osteoblastic differentiation. However, SATB2 is also expressed in other sarcomatous/undifferentiated neoplasms lacking osteoblastic differentiation. Using quantitative reverse transcription PCR (RT-qPCR) we showed that there is variable expression of SATB2 mRNA expression in ATCs. To evaluate the role of SATB2 protein expression in ATC, we performed PAX8, SATB2, pancytokeratin (AE1/AE3 & CAM5.2), claudin-4 and TTF1 immunostaining on 23 cases. ATCs showed retained expression of PAX8 in 65% (15/23); SATB2 was detected in 74% (17/23); pancytokeratin was expressed in 65% (15/23); claudin-4 was expressed in 35% (8/23) and TTF1 showed expression in 13% (3/23) of cases. Furthermore, 83% (5/6) of ATCs which lacked SATB2 expression, retained PAX8 expression, while 88% (7/8) of the tumors without PAX8 expression were positive for SATB2. Differentiated follicular cell-derived thyroid cancers (n = 30), differentiated high grade thyroid carcinoma (n = 3), and poorly differentiated thyroid carcinoma (n = 8) were negative for SATB2 immunoreactivity. Next-generation selected cases detected the commonly identified oncogenic variants including those in BRAF, RAS, TP53, and TERT promoter. Overall, we hereby demonstrate that SATB2 IHC may be used to support the diagnosis of ATC.

Keywords: ATC; Anaplastic thyroid carcinoma; SATB2; Thyroid cancer.

Fig. 1

Hematoxylin–eosin stains of different ATC tumor morphologies observed in our samples: epithelioid (A), spindle cell (B), spindle cell and epithelioid (C), and osteoclast-like multinucleated giant cell rich (D)

Fig. 2

Relative mRNA expression and IHC intensity of SATB2 in ATC tumors and other thyroid malignancies (Poscontrol = colon, Neg control = thyroid, follicular adenoma = FA, follicular thyroid carcinoma = FTC, papillary thyroid carcinoma = PTC, medullary thyroid carcinoma = MTC)

Fig. 3

Hematoxylin–eosin stain and corresponding SATB2 IHC intensity scores for representative ATC tumors samples (A–H) are shown

Fig. 4

Mutations and copy number variations (CNV) identified by in-house NGS (34 gene Oncomine Fusion Assay) in select ATC tumors (n = 13). *TERT promoter and TP53 gene analysis was only available for 5 cases tested by an outside commercial laboratory (FoundationOne)