BACKGROUND: The expressions of galectin-3, cytokeratin 19, p53, and Ki-67 in papillary carcinoma (PC), follicular carcinoma (FC), follicular adenoma (FA), and nodular hyperplasia (NH) are characteristic for the differential diagnosis between benign and malignant thyroid tumors. METHODS: The expressions of the four markers were evaluated in PC (n=37), FC (n=12), FA (n=22), and NH (n=23) by immunohistochemical staining. RESULTS: Statistical analyses revealed that galectin-3 was significantly expressed in the malignant tumor cells of PC and FC, while CK19 was expressed only in PC. CONCLUSION: These results show that galectin-3 is useful in differential diagnosis between malignant and benign thyroid lesions, especially between FC and FA in the patients over 20 years old, and indicate that CK19 is valuable in differentiating between follicular variant of PC and FC and between PC and papillary area of nodular hyperplasia.
Adenoma ; Carcinoma, Papillary ; Diagnosis, Differential* ; Galectin 3* ; Humans ; Hyperplasia ; Keratin-19* ; Keratins* ; Thyroid Gland* ; Young Adult

BACKGROUND: Follicular thyroid carcinoma (FTC) is the second most common thyroid malignancy and its differential diagnosis includes follicular adenoma (FA) and adenomatous goiter (AG). Several ancillary markers have been suggested to aid in the diagnosis of FTC, but the successful use of these methods still needs to be validated. METHODS: In the present study, we verified the immunoexpression of HMGA2, CEACAM6, survivin, and SFN/14-3-3 delta in lesions including 41 AGs, 72 FAs, and 79 FTCs. We evaluated their diagnostic usefulness, combined with galectin 3, Hector Battifora mesothelial 1 (HBME1), cytokeratin 19, and cyclin D1, in diagnosing FTC. RESULTS: The expressions of HBME1 (65.8%) and HMGA2 (55.7%) were significantly higher in FTCs than in FAs and AGs (p<.001 and p=.005, respectively). HBME1 was the only marker that was more frequently expressed in FTCs than in FAs (p=.021) and it was more frequently expressed in follicular neoplasms than in AGs (p<.001). Among the novel markers, the combination of HMGA2 and HBME1 showed the highest sensitivity (72.2%) and specificity (76.1%) for diagnosing FTC. CEACAM6, survivin, and SFN/14-3-3 delta were barely expressed in most cases. CONCLUSIONS: Our present results show that only HMGA2 can be beneficial in differentiating FTC using the novel markers.
Adenocarcinoma, Follicular* ; Adenoma ; Cyclin D1 ; Diagnosis ; Diagnosis, Differential ; Galectin 3 ; Goiter ; Keratin-19 ; Sensitivity and Specificity ; Thyroid Gland

In the last decade, conventional diagnosis of thyroid nodules largely depended on fine-needle aspiration (FNA) and ultrasound. However, FNA has a limited ability to distinguish between benign and malignant lesions, especially in cases with indeterminate cytology. Although the clinical course of differentiated thyroid carcinoma is believed to be favorable, delayed diagnosis can make its clinical management difficult. Many immunohistochemical (IHC) or molecular adjunctive markers have been tested to improve the diagnostic accuracy for thyroid nodules. The common IHC markers galectin-3, Hector Battifora mesothelial-1, and cytokeratin-19 are used alone or as part of panels for both FNA and analysis of surgical specimens. A novel IHC marker, podoplanin, was recently introduced as an adjunctive marker for thyroid cancer diagnosis and prognosis and is associated with the progression of papillary thyroid carcinoma (PTC). Several researchers have identified molecular markers to increase the diagnostic accuracy of thyroid lesions of undetermined significance. Four promising molecular markers have been proposed and thoroughly investigated: B-type Raf kinase (BRAF) and RAS, rearranged in transformation/PTC (RET/PTC), paired box gene 8 (Pax8)/peroxisome proliferator-activated receptor gamma (PPARgamma). BRAF mutations can be measured by immunohistochemistry using an antibody specific to the mutated protein. In this review, we focused on the limitations of current diagnostic tools and on determining the application of the above-mentioned markers to thyroid nodule diagnosis.
Biopsy, Fine-Needle ; Delayed Diagnosis ; Diagnosis ; Galectin 3 ; Immunohistochemistry ; Keratin-19 ; Phosphotransferases ; Prognosis ; Thyroid Gland ; Thyroid Neoplasms* ; Thyroid Nodule ; Ultrasonography

BACKGROUND AND OBJECTIVES: The diagnosis of thyroid nodular diseases is critical for clinical management. Because of the histological similarity of follicular patterned thyroid lesions, the differential diagnosis is often difficult to determine, even with permanent sections. For this reason, we assessed the preoperative diagnostic usefulness of immunohistochemical staining for the four potential markers of malignant thyroid nodule, beta-galactosil binding lectin (Galectin-3), Hector Battifora Mesothelial cell (HBME-1), cytokeratin-19 (CK-19) and high molecular weight cytokeratin (HMW-CK) in tissues obtained by ultrasound-guided core needle biopsy. SUBJECTS AND METHOD: The immunohistochemical expression of Galectin-3, HBME-1, CK-19 and HMW-CK were evaluated in 43 preoperative thyroid lesions obtained to assess their potential as markers in the diagnosis and classification of thyroid malignancy. We compared the preoperative expression of the four markers with the results of postoperative permanent pathology. RESULTS: The expression patterns and positive rates of four markers were the variables in 4 thyroid lesions; however, all markers were strong in malignant thyroid nodules, especially in papillary carcinoma. There were no significant differences in the expression rates of the four markers between follicular carcinoma and follicular adenoma. The sensitivity of HBME-1 for thyroid malignancy was the highest (86%) among the four markers, but the sensitivity of combinational expression using two markers, especially Galectin-3 or HBME-1 (95%), HBME-1 or HMW-CK (90%), was higher than that of the expression using one marker for thyroid malignancy. CONCLUSION: The four markers were reliable markers for papillary carcinoma. In preoperative differential diagnosis of thyroid nodule, we suggest that the combinational expression using two makers is more useful than a single marker expression.
Adenoma ; Biopsy, Large-Core Needle ; Carcinoma, Papillary ; Diagnosis, Differential ; Galectin 3 ; Keratin-19 ; Keratins ; Molecular Weight ; Thyroid Gland ; Thyroid Nodule

BACKGROUND: The incidence of papillary thyroid carcinoma (PTC) has been increasing recently and a precise diagnosis is essential for optimal treatment. Ancillary immunohistochemical stains are important for diagnosing some difficult cases. METHODS: The dignostic value of CD56, high molecular weight cytokeratin (HMCK), galectin-3 (GAL3), and cytokeratin 19 (CK19) were evaluated to distinguish PTC from other benign thyroid lesions (BTL). We studied 23 cases of papillary thyroid overt carcinomas, 57 papillary thyroid microcarcinomas, five follicular adenomas, five cases of Hashimoto's thyroiditis, and 12 nodular hyperplasias. RESULTS: The statistical analysis showed significantly different expressions of CD56, HMCK, GAL3, and CK19 in PTC vs other BTL. The diagnostic specificity of HMCK and CD56 (90.9% and 72.7%, respectively) was higher than that of GAL3 and CK19 (50.0% and 36.4%, respectively). However, the sensitivity of HMCK and CD56 detection (92.5% and 95.0%, respectively) was lower than that of GAL3 and CK19 (98.8% and 100.0%, respectively). The combined use of CD56, HMCK, GAL3, and CK19 showed 87.5% sensitivity, 100.0% specificity, and 100.0% positive predictive value in differentiating PTC from other BTL. CONCLUSIONS: Although the differential diagnosis of thyroid follicular lesions are based on histological and cytomorphological criteria, CD56 and HMCK might be useful markers for diagnosing PTC.
Adenoma ; Carcinoma ; Coloring Agents ; Diagnosis, Differential ; Factor IX ; Galectin 3 ; Incidence ; Keratin-19 ; Keratins ; Molecular Weight ; Sensitivity and Specificity ; Thyroid Gland ; Thyroid Neoplasms ; Thyroiditis

BACKGROUND AND OBJECTIVES: Ancillary tests such as BRAF(V600E) mutation or immunohistochemical (IHC) assays have been utilized as complements to morphological criteria in diagnosing subsets of papillary thyroid carcinoma (PTC). Utilizing results from analysis by The Cancer Genome Atlas (TCGA), we evaluated the diagnostic value and feasibility of these ancillary tests in diagnosing follicular variant PTC (FVPTC). MATERIALS AND METHODS: Clinical data and tissue samples were analyzed from 370 PTC patients, who had undergone thyroidectomy between December 2003 and July 2014. PTC was limited to conventional PTC (CVPTC), tall cell variant PTC (TCPTC), and FVPTC. Using multivariate analyses, FVPTC cases were compared to CVPTC and TCPTC cases. Surgical specimens were pyrosequenced for BRAF(V600E) mutation or stained for IHC markers such as CD56, galectin-3, cytokeratin 19 (CK19), or CD31. For the validation, a comprehensive analysis was performed for BRAF(V600E) mutation and quantitative mRNA expressional difference in TCGA. RESULTS: Demographic differences were not observed between 159 CVPTC, 103 TCPTC, and 108 FVPTC cases. BRAF(V600E) mutation predominated in CVPTC+TCPTC group, but not in FVPTC group (78.4% vs. 18.7%, p<0.001), as suggested by TCGA (57.4% vs. 12.1%, p<0.0001). IHC markers significantly distinguished FVPTC cases from CVPTC+TCPTC cases. CD56 exhibited more intense staining in FVPTC cases (21.1% vs. 72.0%, p<0.001). Galectin-3 and CK19 yielded limited values. CD31 correlated with lymphovascular invasion (r=0.847, p<0.001). In analysis of TCGA, mRNA differential expression of these genes revealed their corresponding upregulation or downregulation. CONCLUSION: BRAF(V600E) mutation or TCGA-validated IHC assay could be recommended as ancillary tests for classifying PTC.
Complement System Proteins ; Down-Regulation ; Galectin 3 ; Genome* ; Humans ; Keratin-19 ; Multivariate Analysis ; RNA, Messenger ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy ; Up-Regulation

Adenocarcinoma ; metabolism ; pathology ; surgery ; Aged ; Cholecystectomy ; Chondrosarcoma ; metabolism ; pathology ; surgery ; Female ; Gallbladder ; chemistry ; pathology ; surgery ; Gallbladder Neoplasms ; metabolism ; pathology ; surgery ; Humans ; Immunohistochemistry ; Keratin-3 ; metabolism ; S100 Proteins ; metabolism

OBJECTIVE: Comparison of protein expressions by two-dimensional gel electrophoresis (2-DE) in normal cervix and squamous cell carcinoma tissues in Korean women. METHODS: Normal cervix and squamous cell carcinoma tissues were solubilized with 2-DE buffer and the first dimension of PROTEAN IEF CELL, isoelectric focusing (IEF), was performed using pH3-10 linear IPG strips of 17 cm. And then running 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and sliver stain. Scanned image was analyzed using PDQuest 2-D softwareTM. Protein spot spectrum was identified by assisted laser desorption/ionization-time of fighting (MALDI-TOF) and the protein mass spectrum identifications were performed by searching protein databases of Swiss-prot/TrEMBL, Mascot and MS-FIT. RESULTS: We found 9 up-regulation proteins (Alpha enolase, Keratin 19 type I, Keratin 20 type I, Keratin 13 type I, beta-actin, Aflatoxin B1 aldehyde reductase 1, Annexin A2, Squamous cell carcinoma antigen 2, unknown), 7 down-reguation proteins (Annexin 1, Myosin regulatory light chain 2, 14-3-3 protein epsilon, Heat shock 27 kDa protein, Hypothetical protein (DKFZP434C1715), Tumor necrosis factor receptor superfamily member 13B, Smoth muscle protein 22-alpha) and 6 up and down-regulation proteins (Tropomyosin 1, Tropomyosin 2, Tropomyosin 3, Serine (or cysteine) proteinase inhibitor, Phosphatidylinositol transfer protein alpha isoform, Src homology 3 domain-containing protein HIP-55) between normal cervix and squamous cell carcinoma cell tissues. CONCLUSION: 2-DE offers total protein expressions between normal cervix and squamous cell carcinoma cell tissues, and searching of differently expressed protein for the diagnostic markers of squamous cell carcinoma tissue.
14-3-3 Proteins ; Actins ; Aflatoxin B1 ; Aldehyde Reductase ; Annexin A2 ; Carcinoma, Squamous Cell ; Cervix Uteri ; Databases, Protein ; Down-Regulation ; Electrophoresis, Gel, Two-Dimensional* ; Electrophoresis, Polyacrylamide Gel ; Female ; Hot Temperature ; Humans ; Isoelectric Focusing ; Keratin-13 ; Keratin-19 ; Keratin-20 ; Mass Spectrometry* ; Muscle Proteins ; Myosin Light Chains ; Phospholipid Transfer Proteins ; Phosphopyruvate Hydratase ; Receptors, Tumor Necrosis Factor ; Running ; Serine ; Shock ; Sodium Dodecyl Sulfate ; Tropomyosin ; Up-Regulation ; Uterine Cervical Neoplasms*

Reports of metastatic hepatocellular carcinoma (HCC) without a primary liver tumor are rare. Here we present a case of isolated HCC that had metastasized to the pelvic bone without a primary focus. A 73-year-old man presented with severe back and right-leg pain. Radiological examinations, including computed tomography (CT) and magnetic resonance imaging (MRI), revealed a huge mass on the pelvic bone (13x10 cm). He underwent an incisional biopsy, and the results of the subsequent histological examination were consistent with metastatic hepatocellular carcinoma. The tumor cells were positive for cytokeratin (AE1/AE3), hepatocyte paraffin 1, and glypican-3, and negative for CD56, chromogranin A, and synaptophysin on immunohistochemical staining. Examination of the liver by CT, MRI, positron-emission tomography scan, and angiography produced no evidence of a primary tumor. Radiotherapy and transarterial chemoembolization were performed on the pelvic bone, followed by systemic chemotherapy. These combination treatments resulted in tumor regression with necrotic changes. However, multiple lung metastases developed 1 year after the treatment, and the patient was treated with additional systemic chemotherapy.
Aged ; Bone Neoplasms/*diagnosis/*pathology/radiotherapy ; Carcinoma, Hepatocellular/*pathology/radiography/*secondary ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Glypicans/metabolism ; Humans ; Keratin-1/metabolism ; Keratin-3/metabolism ; Liver Neoplasms/*pathology/radiography/*secondary ; Magnetic Resonance Imaging ; Male ; Paraffin/metabolism ; Pelvic Bones/*pathology/radiography ; Positron-Emission Tomography ; Tomography, X-Ray Computed

PURPOSE: Our study is performed to find out clinicopathlogic and immunohistochemical (IHC) characteristics of triple negative invasive lobular carcinoma (ILC), as has been demonstrated in their invasive ductal counterparts. MATERIALS AND METHODS: Retrospective analysis of variable clinicopathlogic parameters and IHC stains for androgen receptor, estrogen receptor, progesterone receptor, p53, c-kit, galectin-3, cytokeratin 5 (CK5), CK5/6, vimentin, E-cadherin, epidermal growth factor receptor, and HER2 were performed in 117 cases of ILC. RESULTS: Eight cases (6.8%) were triple negative carcinoma (TNC), which showed higher incidence of high histologic grade than non-TNC (p = 0.019). Galectin-3 was expressed with higher incidence in tumor cells of TNC (62.5%) than those of non-TNC (7.3%) (p = 0.000). In contrast, galectin-3 was expressed with higher incidence in stromal cells of non-TNC (53.2%) than those of TNC (12.5%) (p = 0.029). CK5 and CK5/6 were not expressed in all ILCs. CONCLUSION: TNC in ILC showed distinct clinicopathologic and IHC characteristics such as higher histologic grade and increased expression of galectin-3, compared to non-TNC in ILC. TNC in ILC was less frequent and did not show CK5 and CK5/6 expression when compared to TNC in invasive ductal carcinoma.
Adult ; Breast Neoplasms/*metabolism ; Cadherins/metabolism ; Carcinoma, Lobular/*metabolism ; Female ; Galectin 3/metabolism ; Humans ; Immunohistochemistry/*methods ; Keratin-5/metabolism ; Keratin-6/metabolism ; Middle Aged ; Proto-Oncogene Proteins c-kit/metabolism ; Receptor, Epidermal Growth Factor/metabolism ; Receptors, Androgen ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Vimentin/metabolism