Immunohistochemical analysis based Ep-ICD subcellular localization index (ESLI) is a novel marker for metastatic papillary thyroid microcarcinoma

Kunavisarut, Tada; Kak, Ipshita; MacMillan, Christina; Ralhan, Ranju; Walfish, Paul G.

doi:10.1186/1471-2407-12-523

Cited by 20 publications

(10 citation statements)

References 32 publications

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“…Furthermore, He et al demonstrated the potential of nuclear accumulation of the intracellular domain of EpCAM as a useful marker to distinguish aggressive papillary thyroid carcinoma from non-aggressive types [35]. In addition, the same group reported that nuclear and cytoplasmic intracellular domain of EpCAM and loss of membranous extracellular domain correlate with metastasis in papillary thyroid microcarcinoma [42]. In our present study, the expression of EpCAM was undetectable in FTC-133 and TPC-1 by immunocytochemistry.…”

Section: Discussionsupporting

confidence: 64%

Coexpression of EpCAM, CD44 Variant Isoforms and Claudin-7 in Anaplastic Thyroid Carcinoma

et al. 2014

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BackgroundAnaplastic thyroid cancer is considered to be one of the most aggressive human malignancies, and the mean survival time after diagnosis is approximately six months, regardless of treatments. This study aimed to examine how EpCAM and its related molecules are involved in the characteristics of anaplastic thyroid carcinoma.Methodology/Principal FindingsTwo differentiated thyroid cancer cell lines (TPC-1 and FTC-133), and two anaplastic thyroid cancer cell lines (FRO, ACT-1) were analyzed for expression of CD44 standard isoform (CD44s), CD44 variant isoforms, and EpCAM, and human aldehyde dehydrogenase-1 (ALDH1) enzymatic activity using flow cytometry. CD44s expression was higher in TPC-1 and FTC-133 than in the FRO and ACT-1, whereas ALDH1 activities were higher in FRO and ACT-1 than in TPC-1 and FTC-133. An inverse correlation between CD44s expression and ALDH1 activity was observed in all thyroid cancer cell lines. As for the expressions of CD44 variant isoforms, ACT-1 showed higher and FRO showed moderate CD44v6 expressions, whereas either TPC-1 or FTC-133 showed negative CD44v6 expression. EpCAM expressions in FRO and ACT-1 were higher than those in TPC-1 and FTC-133, and EpCAM expressions inversely correlated with those of CD44s. A positive correlation was observed between EpCAM expression and ALDH1 activity in thyroid cancer cell lines. In the RT-PCR analysis, the expression levels of EpCAM, caludin-7 and ALDH1 in FRO and ATC-1 cells were significantly higher than those in TPC-1 and FTC-133 cells. In clinical specimens of thyroid cancers, nuclear expression of EpCAM and high expression of CD44v6 were detected significantly more frequently in anaplastic carcinomas.Conclusions/SignificanceOur study suggests the possibility that EpCAM, together with CD44v6 and claudin-7 as well as ALDH1, may be involved in the development of the aggressive phenotype of anaplastic thyroid carcinoma. Our findings may suggest a novel therapeutic strategy for treatment of anaplastic thyroid carcinoma.

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Section: Discussionsupporting

confidence: 64%

Coexpression of EpCAM, CD44 Variant Isoforms and Claudin-7 in Anaplastic Thyroid Carcinoma

et al. 2014

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“…Firstly, RIP of EpCAM was not observed in fetal or adult liver cells, nor was it involved in regulating proliferation of these cells [ 148 ]. Secondly, EpICD nuclear translocation in various carcinomas correlated with more aggressive phenotypes and poorer outcome [ 149 – 151 ]. Lastly, generation of EpICD by γ-secretase is a particularly slow process with a 50% turnover of EpCAM-CTF between 0.75 and 5.5 h [ 152 ], as shown for other γ-secretase substrates [ 153 ].…”

Section: Signaling Of Epcammentioning

confidence: 99%

Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?

Gires

Pan

Schinke

et al. 2020

Cancer Metastasis Rev

218

140

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EpCAM (epithelial cell adhesion molecule) was discovered four decades ago as a tumor antigen on colorectal carcinomas. Owing to its frequent and high expression on carcinomas and their metastases, EpCAM serves as a prognostic marker, a therapeutic target, and an anchor molecule on circulating and disseminated tumor cells (CTCs/DTCs), which are considered the major source for metastatic cancer cells. Today, EpCAM is reckoned as a multi-functional transmembrane protein involved in the regulation of cell adhesion, proliferation, migration, stemness, and epithelial-to-mesenchymal transition (EMT) of carcinoma cells. To fulfill these functions, EpCAM is instrumental in intra- and intercellular signaling as a full-length molecule and following regulated intramembrane proteolysis, generating functionally active extra- and intracellular fragments. Intact EpCAM and its proteolytic fragments interact with claudins, CD44, E-cadherin, epidermal growth factor receptor (EGFR), and intracellular signaling components of the WNT and Ras/Raf pathways, respectively. This plethora of functions contributes to shaping intratumor heterogeneity and partial EMT, which are major determinants of the clinical outcome of carcinoma patients. EpCAM represents a marker for the epithelial status of primary and systemic tumor cells and emerges as a measure for the metastatic capacity of CTCs. Consequentially, EpCAM has reclaimed potential as a prognostic marker and target on primary and systemic tumor cells.

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“…Finally, in a series of 36 PTMCs, Kunavisarut et al found a modification of the expression of the epithelial cell molecule (EpCAM) in the papillary cancers. The reduction of the extracellular domain and the increase of the nuclear and cytoplasmic domains of the EpCAM were found to correlate positively with aggressive PTMCs [19]. …”

Section: Discussionmentioning

confidence: 99%

A Papillary Thyroid Microcarcinoma Revealed by a Single Bone Lesion with No Poor Prognostic Factors

Godbert

Henriques-Figueiredo

Cazeau

et al. 2013

Case Reports in Endocrinology

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Objectives. Thyroid carcinomas incidence, in particular papillary variants, is increasing. These cancers are generally considered to have excellent prognosis, and papillary microcarcinomas are usually noninvasive. Many prognostic histopathology factors have been described to guide therapeutic decisions. Most patients are treated with total thyroidectomy without radioiodine treatment or partial surgery. Case Summary. A 65-year-old man with no significant medical history presented with pain in the left chest wall that had been present for several months. A computed tomography (CT) found a large tissue mass of 4 cm responsible for lysis of the middle arch of the 4th rib on the left. It was a single lesion, highly hypermetabolic on the 18-FDG PET/CT. The histology analysis of the biopsy and surgical specimen favored an adenocarcinoma with immunostaining positive for TTF1 and thyroglobulin (Tg). The total thyroidectomy carried out subsequently revealed a 4 mm papillary microcarcinoma with vesicular architecture of the right lobe, well delimited and distant from the capsule without vascular embolisms. After two radioiodine treatments, the patient is in complete clinical, biological, and radiological remission. Conclusion. This extremely rare case of a singular bone metastasis revealing a papillary thyroid microcarcinoma illustrates the necessity of further research to better characterize the forms of papillary thyroid microcarcinomas with potentially poor prognosis.

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Immunohistochemical analysis based Ep-ICD subcellular localization index (ESLI) is a novel marker for metastatic papillary thyroid microcarcinoma

Cited by 20 publications

References 32 publications

Coexpression of EpCAM, CD44 Variant Isoforms and Claudin-7 in Anaplastic Thyroid Carcinoma

Coexpression of EpCAM, CD44 Variant Isoforms and Claudin-7 in Anaplastic Thyroid Carcinoma

Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?

A Papillary Thyroid Microcarcinoma Revealed by a Single Bone Lesion with No Poor Prognostic Factors

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