emerin and Thyroid-Neoplasms

Papillary thyroid carcinoma (PTC) is diagnosed in both cytological and histological specimens on the basis of distinct nuclear morphology. These features may not be prominent in some PTC variants and may be seen in some benign conditions. It is necessary to differentiate PTC from other neoplastic and nonneoplastic lesions since it affects treatment strategy and patients' fate. Emerin is a type II integral membrane protein of the inner nuclear membrane that has a characteristic staining pattern in PTC. CD56 is a homophilic membrane glycoprotein that is expressed in thyroid follicular epithelial cells and adrenal glands. The aim of this study was to evaluate the diagnostic value of emerin (positivity, percentage, and highlighting nuclear features) and CD56 (positive versus negative) both singly and in combination for differentiation of PTC from other neoplastic and nonneoplastic mimics. This study was performed on 50 cases of PTC, 9 cases of follicular adenoma (FA), and 12 cases of nonneoplastic thyroid lesions using immunohistochemistry for detection of emerin and CD56. Positive emerin expression was seen in 82% of PTC and in 16.7% of nonneoplastic cases with an absence of expression in FA. CD56 was expressed in 88.9% of FA, 91.7% of nonneoplastic cases and in a minority of PTC cases (6%). Positive emerin revealed 82% sensitivity and 90% specificity, while emerin-highlighted nuclear changes was more specific (95%). Negative CD56 expression revealed 84% sensitivity and 90% specificity. Combined positive emerin (including highlighting nuclear changes) and negative CD56 showed 72% sensitivity and 100% specificity. Positive emerin expression (moderate/strong) and its highlighting nuclear changes combined with negative CD56 could be a very helpful procedure in difficult and overlapping cases with high diagnostic validity (high specificity and positive predictive value).

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Carcinoma, Papillary; CD56 Antigen; Child; Female; Humans; Immunohistochemistry; Male; Membrane Proteins; Middle Aged; Nuclear Proteins; Retrospective Studies; Thyroid Cancer, Papillary; Thyroid Neoplasms; Young Adult

Recently, it has been reported that identifying nuclear membrane irregularities with anti-emerin antibody is useful for papillary thyroid carcinoma diagnosis. However, literature regarding the significance of emerin immunohistochemistry in thyroid is limited. We evaluated the diagnostic accuracy of the well-established nuclear alterations, nuclear protrusions and recently described nuclear shapes (garlands and star-like shapes) with emerin immunohistochemistry and hematoxylin- eosin stain in thyroid lesions. We further evaluated the diagnostic accuracy measures of tissue microarrays evaluated with both stains, to detect whether emerin immunohistochemistry improves the diagnostic accuracy for papillary thyroid carcinoma. For papillary thyroid carcinoma, pseudo- inclusions were best performers with emerin (diagnostic accuracy: 0.91), whereas with hematoxylin- eosin diagnostic accuracy of grooves was the highest (0.92). For follicular variant of papillary thyroid carcinoma, with both stains, predominately oval nuclear shape had the best diagnostic performance (diagnostic accuracy: 0.95). Nuclear protrusions were poor identifiers for papillary thyroid carcinoma. However, with emerin immunohistochemistry, they could successfully identify malignancy in 83% of the cases. Using emerin immunohistochemistry, in addition to hematoxylin- eosin improved the diagnostic accuracy for papillary thyroid carcinoma when compared to hematoxylin- eosin evaluation only (sensitivity: 0.70 vs 0.86, negative predictive value: 0.81 vs. 0.94, diagnostic accuracy: 0.87 vs. 0.94). Consistent with the previous literature, our findings indicate that emerin immunohistochemistry may be used as an adjunct diagnostic method to identify papillary thyroid carcinoma. Additionally, we suggest that nuclear protrusions detected with emerin imunohistochemistry may be used as indicators of malignant behavior in small tissue samples of thyroid.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma; Carcinoma, Papillary; Cell Differentiation; Epithelial Cells; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Membrane Proteins; Nuclear Proteins; Predictive Value of Tests; Retrospective Studies; Sensitivity and Specificity; Thyroid Cancer, Papillary; Thyroid Neoplasms

Emerin, lamin A/C, lamin B, and lamin-associated polypeptide 2 (LAP2) are nuclear membrane proteins that play an important role in maintaining nuclear structure and coordinating cell activity. We studied the expression and significance of nuclear membrane proteins in neoplastic thyroid cells by immunohistochemistry, RT-PCR, and real-time PCR. In papillary carcinomas (PCs), the nuclear proteins most frequently expressed at high levels were emerin (82 % positive), lamin A/C (64 %), and LAP2 (82 %). Follicular carcinomas (FCs) most frequently expressed lamin B, while none of the undifferentiated carcinomas (UCs) showed strong expression of emerin or lamin A/C. In all medullary carcinomas (MCs), intermediate to high levels of expression of lamin A/C and LAP2 were found. By RT-PCR analysis, messenger RNA (mRNA) expression of all nuclear membrane proteins except emerin was higher in PC than in normal tissue. Real-time PCR analysis showed that mRNA expression of nuclear membrane protein varied between cell lines. Our findings suggest that expression of nuclear membrane proteins may be related to follicular function in normal and hyperplastic follicles, and we hypothesize that they are also involved in the proliferation and differentiation of neoplastic thyroid cells. We suggest that they reflect the biological nature and/or function of normal, hyperplastic, and neoplastic thyroid cells and may have some value in diagnosing thyroid tumors.

Topics: Cell Line, Tumor; DNA-Binding Proteins; Epithelial Cells; Humans; Hyperplasia; Immunohistochemistry; Lamin Type A; Lamin Type B; Membrane Proteins; Nuclear Proteins; Real-Time Polymerase Chain Reaction; Thyroid Gland; Thyroid Neoplasms

Immunohistochemical staining (IHC) with emerin, an integral inner nuclear membrane protein, highlights nuclear membrane details in papillary thyroid carcinoma (PTC). We evaluated emerin for highlighting nuclear shape, grooves, inclusions, circumferential nuclear membrane irregularities ("garlands"), deep "stellate" membrane invaginations, and crescents in 34 fine-needle aspiration (FNA) cell blocks, PTC (n = 24) and follicular neoplasms (FN) (n = 10). Tissue microarrays were also examined for 182 cases, PTC (n = 95) and non-PTC (n = 87). Emerin IHC of PTC revealed a predominantly oval nuclear shape in the majority of cases, with FN demonstrating round nuclei and FV of PTC showing a roughly equal distribution of round and oval shapes. In addition to oval nuclear shape, the presence of emerin-positive nuclear grooves, circumferential emerin nuclear "garlands," nuclear crescent shapes, and chromatin clearing on cell block H&E staining were significant predictors of PTC by regression analysis. Emerin IHC of thyroid FNA and surgical specimens serves as a useful adjunct to conventional H&E staining in the diagnosis of PTC and its distinction from FN by delineating diagnostic nuclear membrane irregularities ("garlands" and crescents), nuclear grooves, and a characteristic oval nuclear shape. In diagnostically challenging cases with limited cellularity, emerin staining can help to provide a more definitive diagnosis of PTC.

Topics: Carcinoma, Papillary; Cell Nucleus; Humans; Membrane Proteins; Nuclear Envelope; Nuclear Proteins; Thyroid Neoplasms

Decoration of the nuclear membrane by emerin staining enhances detection of nuclear irregularities typical of papillary thyroid carcinoma (PTC). Our study aims to verify whether staining with emerin is a helpful diagnostic marker in fine-needle aspiration (FNA) cytology. We first designed a prospective study on smears, Thin Prep, and cell block specimens to prove the feasibility of the procedure; subsequently, we designed a retrospective study of 78 FNA cell blocks from cases that, after surgery, turned out to be either benign (34 cases) or malignant lesions (44, of which 31 PTC). From each sample, we obtained two slides, one stained with hematoxylin and eosin (H&E) and the other with emerin. In cases classified as Thy3, HBME-1 and galectin 3 (Gal3) stains had also been performed. Two blinded observers made the judgment concerning Thy categories (as proposed by the British Thyroid Association), first on H&E, then on emerin, HBME-1, and Gal3 stained slides. On cytological preparation, emerin staining represents an effective tool for the detection of nuclear irregularities, allowing for the identification of cases of PTC. In Thy3 cases, emerin staining's sensitivity and specificity (64% and 96%) proved higher than HBME-1's (60% and 88%) and Gal3's (61% and 68%). In conclusion, the immunohistochemical definition of the nuclear membrane, as determined by emerin stain, is a useful tool in the cytological diagnosis of thyroid lesions and can help to solve inconclusive cases by highlighting nuclear irregularities typical of PTC.

Topics: Adenocarcinoma, Papillary; Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biopsy, Fine-Needle; Cytodiagnosis; Female; Humans; Male; Membrane Proteins; Middle Aged; Nuclear Envelope; Nuclear Proteins; Retrospective Studies; Sensitivity and Specificity; Staining and Labeling; Thyroid Neoplasms; Young Adult

Objective appreciation of irregularities of the nuclear shape is a key parameter in the diagnosis of thyroid lesions, since foldings of the nuclear membrane (NM) featuring indentations, grooves and pseudoinclusions characterize papillary thyroid carcinomas (PTC). The aim was to focus on the immunohistochemistry of emerin, a protein of the NM whose decoration best demarcates the nuclear shape.. Immunohistochemistry of the NM with emerin as well as three-dimensional reconstruction of the images (through deconvolution processing) performed on a series of 54 cases (processed following the tissue array procedure) revealed a uniform arrangement of the NM in non-neoplastic lesions (thyroiditis, microfollicular goitre, follicular adenoma) and normal thyroid as well as in follicular carcinoma. In contrast, irregular folding of the membrane and presence of curling and invaginations, eventually leading to the formation of nuclear pseudoinclusions, was observed in PTC cells.. Decoration of the NM represents an original approach to identify PTC nuclear shape, highlights new structural features and might be helpful in the differential diagnosis between so-called nuclear pseudoinclusions and artefactual 'bubbles'.

Topics: Adenocarcinoma, Papillary; Diagnosis, Differential; Fluorescent Antibody Technique; Humans; Image Interpretation, Computer-Assisted; Immunohistochemistry; Membrane Proteins; Nuclear Envelope; Nuclear Proteins; Thyroid Diseases; Thyroid Neoplasms; Tissue Array Analysis

Papillary thyroid carcinomas (PTCs) have characteristic nuclear shape changes compared to follicular-type thyroid epithelium. We tested the hypothesis that the altered nuclear shape results from altered distribution or expression of the major structural proteins of the nuclear envelope. Lamin A, lamin B1, lamin C, lamin B receptor (LBR), lamina-associated polypeptide 2 (LAP2), emerin, and nuclear pores were examined. PTC's with typical nuclear features by H&E were compared to non-neoplastic thyroid and follicular neoplasms using confocal microscopy, and semi-quantitative immunoblotting. Lamin A/C, lamin B1, LAP2, emerin, and nuclear pores all extend throughout the grooves and intranuclear inclusions of PTC. Their distribution and fluorescent intensity is not predictably altered relative to nuclear envelope irregularities. By immunoblotting, the abundance (per cell) and electrophoretic mobilities of lamin A, lamin B1, lamin C, emerin, and LAP2 proteins do not distinguish PTC, normal thyroid, or follicular neoplasms. These results do not support previously published predictions that lamin A/C expression is related to a loss of proliferative activity. At least three LAP2 isoforms are identified in normal and neoplastic thyroid. LBR is sparse or undetectable in all the thyroid samples. The results suggest that the irregular nuclear shape of PTC is not determined by these nuclear envelope structural proteins per se. We review the structure of the nuclear envelope, the major factors that determine nuclear shape, and the possible functional consequences of its alteration in PTC.

Topics: Blotting, Western; Carcinoma, Papillary, Follicular; Cell Fractionation; Centrifugation, Density Gradient; Electrophoresis; Fluorescent Antibody Technique, Direct; Humans; Isomerism; Laminin; Membrane Proteins; Microscopy, Confocal; Nuclear Envelope; Nuclear Proteins; Thymopoietins; Thyroid Neoplasms; Tissue Fixation