TROP-2, 5hmC, and IDH1 Expression in Anaplastic Thyroid Carcinoma

Abstract

Background Anaplastic thyroid carcinoma (ATC), a highly aggressive malignancy, has no effective treatment to date. Trophoblast cell-surface antigen 2 (TROP-2), a transmembrane glycoprotein, has been suggested to be a promising novel target for sacituzumab govitecan, an antibody-drug conjugate. 5-Hydroxymethylcytosine (5hmC) has a role in tumor suppression and promoting modification. Additionally, isocitrate dehydrogenase 1 (IDH1) mutations are strongly associated with increased overall survival in gliomas and worse prognosis in leukemias. This study attempts to evaluate the immunoexpression of TROP-2, 5hmC, and IDH1 in ATCs and to determine their potential impact in targeted therapy. Methods Twenty-four ATCs were retrieved, with 9 cases that occurred de novo and 15 cases derived from either papillary thyroid carcinoma (PTC) or follicular thyroid carcinoma (FTC). Sections were immunostained with TROP-2, 5hmC, and IDH1 antibodies, and evaluated using the QuPath program. The t tests were performed using SPSS software. Results TROP-2 was detected in 12 ATCs with 9 cases demonstrating a high expression and in all PTC components, and absent in all FTC components of secondary ATCs. 5hmC expression was moderately reduced in PTC and FTC components and markedly reduced in ATC. The entire cohort showed a total absence of IDH1. Conclusions Increased TROP-2 immunoexpression in some ATCs supports that these patients may potentially benefit from an antibody-drug conjugate therapy targeting TROP-2. Markedly reduced 5hmC expression suggests that 5hmC may be used as potential therapeutic targets for ATC. The total lack of IDH1 R132H mutation by immunostain indicates that it has no prognostic and therapeutic value in ATC.

Trop-2 Therapy in Metastatic Triple-Negative Breast Cancer in Italy: Clinical Opportunity and Regulatory Pitfalls

“…Despite the several limitations of this study, such as inconsistency in Trop-2 detection and criteria of Trop-2 positivity, the authors stated that a frequent Trop-2 expression in the majority of solid tumors and its association with a poor prognosis provided a good rationale to target Trop-2 for therapeutic purposes [18]. Trop-2 expression has also been described in some rare and aggressive malignancies, such as salivary duct carcinomas [19], anaplastic thyroid carcinomas [20], uterine/ovarian carcinosarcomas [21,22], and neuroendocrine carcinoma (NEC) of the prostate [23]. In prostate (NEC), Trop-2 seems to closely interplay with the Poly ADP-ribose polymerase enzyme promoting neuroendocrine phenotype and aggressiveness of prostate cancer [24].…”

The role of 5-hydroxymethylcytosine as a potential epigenetic biomarker in a large series of thyroid neoplasm

“…The role of 5-hmC in thyroid tumours remains to be clari ed. There are few studies, and some data begin to emerge, based on relatively small and unrepresentative series, regarding tumour pattern diversity [13][14][15][16]. In a cohort, only including papillary thyroid carcinomas (PTCs) (n = 88) and multinodular goiter (MNG) (n = 20) cases, Tong et al, described the decreased level of 5-hmC in PTC tumour samples from patients with lymph node metastasis, when compared to PTC tumour samples from patients without lymph node metastasis [13].…”

TROP-2, Nectin-4, GPNMB, and B7-H3 Are Potentially Therapeutic Targets for Anaplastic Thyroid Carcinoma

“…In addition, some clinical trials of ADCs targeting proteins on cell membranes, such as glycoprotein non-metastatic B (GPNMB) and B7-H3, are currently in progress [12,13]. TROP-2 was detected in 50% of 24 ATC cases [14], and HER2 expression has been rarely observed in ATC cases [15,16]. However, no studies have evaluated the expression of other ADC target proteins, such as nectin-4, GPNMB, and B7-H3 in ATCs.…”