Galectin-3 expression in papillary microcarcinoma of the thyroid

AIMS: Galectin-3 is a beta-galactoside binding protein, recently recognized as a promising molecular marker of thyroid malignancy. As reported in several studies, galectin-3 is highly expressed in papillary thyroid carcinoma, but its expression has not been investigated in papillary microcarcinoma, which is a variant of papillary thyroid carcinoma. METHODS AND RESULTS: Using a monoclonal antibody to galectin-3 and the avidin-biotin-peroxidase complex (ABC) immunohistochemical technique, we analysed galectin-3 expression in 63 cases of papillary microcarcinoma. The results showed immunohistochemical reactivity for galectin-3 in 51 (80.9%) cases. Intensity of staining varied from strong or moderate to weak. Galectin-3 localization was mostly cytoplasmic, but also membranous or nuclear in some cells. Immunohistochemical expression of galectin-3 was not found in 12 (19.1%) cases. Most galectin-3 negative microcarcinomas (10/12) were of the non-classical type, i.e. without papillary architecture. Neither the frequency nor the intensity of a positive reaction was related to tumour size. CONCLUSIONS: Galectin-3 gene is expressed at the protein level in most papillary microcarcinomas, although with slightly lower frequency than that reported for clinically evident papillary thyroid carcinoma. The presence of galectin-3 in clinically silent microcarcinomas may indicate that galectin-3 is not related to growth or aggressiveness of papillary thyroid microcarcinomas but rather plays some other role in thyroid tumour biology.     

Overcoming the Limitations of Fine Needle Aspiration Biopsy: Detection of Lateral Neck Node Metastasis in Papillary Thyroid Carcinoma

Purpose

Ultrasound (US) and US-guided fine needle aspiration biopsies (FNAB) are considered the modalities of choice for assessing lymph nodes suspected of containing metastases, but the sensitivity of FNAB varies and is specific to the operator. We analyzed the risk of FNAB providing false negative results of lateral neck node metastasis, and evaluated diagnostic accuracy of FNAB, in patients with papillary thyroid cancer.

Materials and Methods

FNAB was performed in 242 patients suspected of having lateral neck node metastasis on preoperative imaging. Thyroglobulin in the fine-needle aspirate washout (FNA wash-out Tg) and computed tomography enhancement (Hounsfield units) were measured. Patients with negative results on FNAB were examined by intraoperative frozen section. The false negative and true negative groups were compared.

Results

Of the 242 patients, 130 were confirmed as having lateral neck node metastases. In 74 patients, the metastasis was identified by FNAB. False positive results were observed in 2 patients (0.8%) and false negatives in 58 (44.6%). Risk analysis showed that patient age <45 years (p=0.006), tumor size >1 cm (p=0.008) and elevated FNA wash-out Tg (p=0.004) were significantly associated with false negative results on FNAB. The accuracy of FNAB increased significantly when combined with FNA wash-out Tg (p=0.003).

Conclusion

To reduce the false negative rate of FNAB, patient age (<45 years), tumor size (>1 cm) and FNA wash-out Tg (>34.8 ng/mL) should be considered in preoperative planning. Accuracy may be improved by combining the results of FNAB and FNA wash-out Tg.     

Retracted: Alpinumisoflavone Inhibits Tumor Growth and Metastasis in Papillary Thyroid Cancer via Upregulating miR-141-3p

Alpinumisoflavone (AIF) as a principal active ingredient of traditional Chinese herb Derris eriocarpa exerts a broad spectrum of anticancer activities against solid tumors. However, little is known about the effect of AIF on papillary thyroid cancer (PTC). Objectives of this study are to investigate the effect of AIF on cell growth, apoptosis, and metastasis of PTC cells and uncover its underlying mechanisms. Results showed that AIF treatment notably suppressed cell viability, migration, invasion, and epithelial–mesenchymal transition (EMT) process, as well as induced apoptotic cell death. In addition, microarray analysis results revealed that miR-141-3p level was dramatically elevated upon AIF insulation, suggesting that miR-141-3p may mediate the suppressive role of AIF against PTC. Moreover, miR-141-3p knockdown effectively reversed the effects of AIF on cell growth, migration, invasion, and EMT, while promoted PTC cell apoptosis escape. Furthermore, in vivo findings also confirmed that the antigrowth and antimetastasis activities of AIF were, at least partly, mediated by upregulation of miR-141-3p. Overall, AIF could serve as a potential anticancer compound for PTC treatment. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1842–1850, 2020. © 2019 American Association for Anatomy     

Carbohydrate Antigens as Oncofetal Antigens in Papillary Carcinoma of the Thyroid Gland

The expression of simple mucin-type antigens, Lewis type-1 antigens, and Lewis type-2-related antigens was evaluated by immunohistochemistry in a series of nine fetal thyroid glands. The aim of the study was to establish whether the previously reported expression of carbohydrate antigens in thyroid carcinomas represents a “de novo” expression or a form of the so-called oncofetal expression. We have detected simple mucin-type antigens and Lewis type-2-related antigens in fetal thyroid tissue. Lewis type-1 antigens were not found. Taking the results of this study together with those previously reported, we conclude that the presence of Lewis type 1 antigens in thyroid carcinomas appears to be a “de novo” expression, whereas the constant and strong expression of simple mucin-type antigens and Lewis type-2-related antigens represents a reexpression (oncofetal expression) of antigens already present during fetal life.     

甲状腺乳头状癌颈部淋巴结转移特点及相关危险因素分析

目的 探讨甲状腺乳头状癌（PTC）临床病理特征及影响颈部淋巴结转移的危险因素。方法 回顾性分析我院2015年1月~2017年12月收治的515例PTC的临床资料,分析颈部淋巴结转移特点及相关危险因素。结果 PTC颈部淋巴结转移率为44.27%,中央组（Ⅵ区）淋巴结转移率高于侧区（P＜0.05）。单因素分析结果示性别、年龄、多灶、癌灶最大径、侵犯被膜和颈部淋巴结转移有关（P＜0.05）。多因素分析结果示男性、年龄＜55岁、多灶病变、癌灶最大径＞10 mm、被膜受侵犯是发生颈部淋巴结转移的独立危险因素（P＜0.05）。结论 Ⅵ区转移率最高,行颈淋巴结清扫时应将Ⅵ区作为常规清扫区域。对于男性、年轻、多灶病变、癌灶最大径＞10 mm、被膜受侵犯的患者应高度警惕颈部淋巴结转移的可能。     

Clinicopathological and Molecular Histochemical Review of Skull Base Metastasis from Differentiated Thyroid Carcinoma

Skull base metastasis from differentiated thyroid carcinoma including follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) is a rare clinical entity. Eighteen FTC cases and 10 PTC cases showing skull base metastasis have been reported. The most common symptom of skull base metastasis from FTC and PTC is cranial nerve dysfunction. Bone destruction and local invasion to the surrounding soft tissues are common on radiological imaging. Skull base metastases can be the initial clinical presentation of FTC and PTC in the presence of silent primary sites. The possibility of skull base metastasis from FTC and PTC should be considered in patients with the clinical symptoms of cranial nerve dysfunction and radiological findings of bone destruction. A variety of genetic alterations in thyroid tumors have been identified to have a fundamental role in their tumorigenesis. Molecular histochemical studies are useful for elucidating the histopathological features of thyroid carcinoma. Recent molecular findings may provide novel molecular-based treatment strategies for thyroid carcinoma.     

Combined "Mixed Medullary-Follicular" and "Papillary" Carcinoma of the Thyroid with Lymph Node Metastasis

We report a case of combined “mixed medullary-follicular” and “papillary” carcinoma of the thyroid that occurred in a 44-yr-old Japanese woman. The grossly single 3 cm tumor was histologically composed of both mixed medullary-follicular carcinoma and papillary carcinoma, which abutted against each other with a clear border between two components. Immunohistochemically, the component of medullary carcinoma was positive for calcitonin and carcinomebryonic antigen (CEA), and the follicular carcinoma and papillary carcinoma components were positive for thyroglobulin. Lymph node metastasis was also noted. The patient has been alive without recurrence for 20 yr. To the best of our knowledge, this is the first reported case in the literature. We report this unique case of thyroid carcinoma and review related thyroid malignancies.     

Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms

AIMS: To determine whether galectin-3 is a sensitive indicator of thyroid malignancy. It has been suggested as a potential marker for differentiating thyroid carcinoma from benign or non-neoplastic lesions in preoperative fine-needle aspirates (FNAs). METHODS: Galectin-3 protein expression was assessed by immunohistochemistry in formalin-fixed thyroid tissues from 124 patients with histological diagnoses of papillary carcinoma (n = 38), follicular carcinoma (n = 19), follicular adenoma (n = 32) and dominant nodules of multinodular goitre (n = 35). Expression of galectin-3 was also assessed by Western blotting in 24 fresh thyroid tissues. RESULTS: Galectin-3 expression was observed in the majority of carcinomas (papillary 92%; follicular 74%). However, a large proportion of follicular adenomas (72%) and multinodular goitres (57%) also expressed galectin-3. In addition, galectin-3 expression was observed in epithelial cells of normal thyroid tissue and Hashimoto's thyroiditis. Galectin-3 immunopositivity was significantly greater in papillary carcinomas than in dominant nodules or follicular adenomas (P < 0.0001, P = 0.0005, respectively). However, galectin-3 expression was no greater in follicular carcinomas than in follicular adenomas (P = 0.8735). Western blotting analysis confirmed both the specificity of the antiserum and expression of galectin-3 in multinodular goitres, follicular adenomas/carcinomas and papillary carcinomas. CONCLUSION: The data demonstrate that galectin-3 is not a reliable immunohistochemical marker to distinguish benign from malignant thyroid follicular lesions.     

Differential Expression Profiling and Functional Analysis of microRNAs through Stage I-III Papillary Thyroid Carcinoma

Objective: To elucidate the mechanisms undergoing the pathogenesis of PTC, this study try to find stage specific microRNAs (miRNAs) using microarray chip in stage I, II and III papillary thyroid carcinoma (PTC) tissues as well predict miRNAs binding target genes and their molecular functions.Methods: PTC specimens of stage I, II, and III and their paired adjacent non-tumor tissue (one patient for each stage) were collected. The expressions of miRNAs were examined using miRNA microarray chip. The most significant changed miRNAs from microarray were verified by using quantitative RT-PCR. The Potential miRNAs regulating target genes and their preliminary biological functions were forecasted with variety function prediction software.Results: Ten miRNAs exhibited sequential up regulation expression profiles and five miRNAs performed sequential down regulation throughout stage I to III (p<0.05). After normalization, Fifteen miRNAs showed significant different compared to adjacent non-tumor tissues (p<0.05). Among of them, the most significant up regulation and down regulation miRNAs were miR-146b-5p and miR-335, respectively. Both of them were verified with qRT-PCR. 34 target genes for miR-146-5p and 36 target genes for miR-335 was predicted.Conclusion: MicroRNA profile assay successfully detected a branch of differential expression miRNAs between PTC and normal tissue. Some of them also showed stage specific. Biological function analysis showed that target genes were involved in five aspects including cell proliferation, differentiation, apoptosis, cycle, and signaling transduction pathway, suggesting the regulatory role of abnormal expression of critical miRNAs in the pathogenesis of PTC.     

Metastatic Follicular Variant of Papillary Thyroid Carcinoma Manifested as a Primary Renal Neoplasm

Although autopsies performed on patients with cancer have shown 4.6 to 7.6% of metastases to the kidneys, the preoperative clinical identification remains rare. The primary sources of metastases to the kidney are in decreasing order of frequency: breast, lung, intestine, contralateral kidney, stomach, ovary, cervix, pancreas, uterus, and prostate. As far as we know, only seven cases of malignant neoplasms of the thyroid gland metastatic to the kidney have been reported [1]. Herein, we report the eighth case of this event and the second of a follicular variant of papillary thyroid carcinoma whose initial manifestation was hematuria and flank pain.     

Pathologic Spectrum of Lymphocytic Infiltration and Recurrence of Papillary Thyroid Carcinoma

Purpose

The aim of this study was to investigate the prognosis of papillary thyroid carcinoma (PTC) patients according to different pathologic grades of lymphocytic thyroiditis (LT).

Materials and Methods

This study included 144 PTC patients who underwent total thyroidectomy with radioactive iodine remnant ablation therapy. Pathologic grades of LT were separated at two points, chronic lymphocytic thyroiditis (CLT) and Hashimoto thyroiditis (HT). Patients were divided into two groupings according to the presence of the diseases (Grouping 1; patients with CLT or HT and without CLT or HT, Grouping 2; patients with HT and without HT). The groupings were compared according to recurrence, clinicopathologic and ultrasound (US) characteristics, and disease free survival.

Results

Of 144 patients, 41 had CLT and 19 had HT. There were 10 patients (6.9%) with tumor recurrence. In both groupings, the presence of calcification was more frequently associated with patients with LT (p=0.041 and 0.047, respectively). In Grouping 2, the mean age at diagnosis was older in patients without HT compared to patients with HT (p=0.032). On multivariate analysis, the presence of LT was not an independent predictor of recurrence in both groupings. For both groupings, pathologic tumor size and taller than wide shape on US were independent predictors of recurrence. The presence of LT in PTC patients did not affect recurrence.

Conclusion

There was no relationship between PTC prognosis and different grades of LT. Pathologic tumor size and taller than wide shape on ultrasound were independent predictors of PTC recurrence regardless of concurrent LT.     

Interleukin-1 Beta Polymorphisms are Associated with Lymph Node Metastasis in Korean Patients with Papillary Thyroid Carcinoma

In this study, we investigated whether single nucleotide polymorphisms (SNPs) of the interleukin-1 beta (IL-1B) were associated with papillary thyroid carcinoma (PTC). We also assessed the relationships between IL-1B SNPs and the clinicopathologic characteristics of PTC patients. Ninety-three PTC patients and 324 controls were recruited. The patients with PTC were dichotomized and compared with respect to the clinicopathologic characteristics of PTC. Seven SNPs in the IL-1B gene were selected and genotyped using direct sequencing. Four SNPs (rs1143627, rs3136558, rs1143633, and rs1143643) in the IL-1B gene were significantly associated with PTC (p < 0.05). In clinicopathologic features, 3 SNPs (rs1143630, rs1143633, and rs1143643) showed a strong relationship with lymph node metastasis of PTC. The genotype and allele frequencies of rs1143630 and rs1143643 remained significantly associated with lymph node metastasis after Bonferroni correction for multiple testing. In haplotype analysis, two linkage disequilibrium blocks (block 1 consisted of rs1143627, rs3917356, and rs1143630; block 2 consisted of rs1143633 and rs1143643) also revealed significant associations with lymph node metastasis. Our results suggest that IL-1B polymorphisms may be associated with the risk of PTC in the Korean population. Especially, IL-1B polymorphisms might be a predictive factor for lymph node metastasis of PTC patients.     

Macrofollicular Variant of Papillary Thyroid Carcinoma: A Case and Control Analysis

The planimetric, flow cytometric, and immunohistochemical characteristics of the macrofollicular variant of papillary thyroid carcinoma (MFVPTC) have not been reported before. The clinical, morphological, immunohistochemical, planimetric, and flow cytometric characteristics of six cases of the MFVPTC and six of the follicular variant of papillary thyroid carcinoma (FVPTC) were analyzed. Patients had undergone surgical treatment. The mean age was 38 (range 29–64 yr), and five were women. Tumors had a mean size of 3.2 cm (range 0.3–4.5 cm). Half were originally diagnosed as goiter. Macrofollicles had a mean diameter of 345.5 μm, perimeter of 1237 μm, and area of 13,779 μm², with nuclear changes of PTC. Mean follow-up was 107 mo (range 12–277), and neither lymph node metastases nor recurrence were seen. Differences in diameter, perimeter, and area between the macrofollicular and follicular variants were found. Follicular neoplastic cells were thyroglobulin and S-100 protein positive in macrofollicles and normofollicles. All were negative to cytokeratin and to high-mol-wt keratin. All tumors were diploid. There were no significant differences in follow-up, DNA content, nor immunohistochemical reactivity. Differences in diameter (p<0.00006), perimeter (p<0.0001), and area (p<0.001) were observed. It is important to recognize this variant because it could be misdiagnosed as benign thyroidal lesions. Part of this work was presented as a poster at the 85th Annual Meeting of the United States and Canadian Academy of Pathology in Washington, DC, March 1996.     

Detection of Plasma BRAFV600E Mutation Is Associated with Lung Metastasis in Papillary Thyroid Carcinomas

Purpose

The BRAF^V600E mutation represents a novel indicator of the progression and aggressiveness of papillary thyroid carcinoma (PTC). The purpose of this study was to determine the clinical significance of free circulating mutant BRAF^V600E in predicting the advanced disease of PTC.

Materials and Methods

Seventy seven matched tumor and plasma samples obtained from patients with both benign and PTC were analyzed for BRAF^V600E mutation using a peptide nucleic acid (PNA) clamp real-time polymerase chain reaction (PCR).

Results

The BRAF^V600E mutation was absent in tumor DNA samples obtained from patients with benign follicular adenomas or adenomatous goiter. In contrast, 49 of 72 (68.1%) PTC tumors were positive for the BRAF^V600E mutation. Among them, 3 (6.1%) patients with PTC were positive for BRAF^V600E mutation in plasma and tumor. However, all 3 patients (100%) had lateral lymph node and lung metastasis.

Conclusion

These findings suggest that the BRAF^V600E mutation can be detected using a PNA clamp real-time PCR in the blood of PTC patients with lung metastasis. Future studies are warranted to determine clinical significance of serum BRAF^V600E mutation in large prospective studies.     

The Cytoplasmic Expression of MUC1 in Papillary Thyroid Carcinoma of Different Histological Variants and its Correlation with Cyclin D1 Overexpression

This study addressed the immunohistochemical expression of MUC1 in papillary thyroid carcinoma (PTC) of different histotypes, sizes, and morphological features of aggressiveness, and its correlation with the overexpression of cyclin D1, a target molecule of the Wnt pathway. MUC1 expression was examined in a total of 209 PTCs. Cytoplasmic MUC1 expression was elevated in the tall, columnar cell and oncocytic variants (100%), Warthin-like (78%), and conventional PTCs (61%), and in papillary microcarcinoma (PMC) with the conventional growth pattern (52%). On the contrary, it was low in the follicular variant (27%) of PTC and PMCs with follicular architecture (13%). Cytoplasmic MUC1 accumulation did not associate with any clinicopathological features except peritumoral lymphoid infiltration in PTCs and in PMCs with the conventional growth pattern. MUC1 staining correlated with cyclin D1 overexpression in conventional PTCs and PMCs and PMCs with follicular architecture. The results demonstrate that MUC1 expression varies broadly in different histological variants of PTC, being the lowest in tumors with follicular structure. In general, it does not prove to be a prognosticator of PTC aggressiveness. A high correlation between MUC1 and cyclin D1 implies MUC1 involvement in the Wnt cascade functioning in a large subset of human PTCs and PMCs.     

Immunohistochemical Demonstration of Membrane-bound Prostaglandin E2 Synthase-1 in Papillary Thyroid Carcinoma

Microsomal prostaglandin E₂ synthase-1 (mPGES-1) is an inducible enzyme that catalyzes the conversion of prostaglandin (PG) H₂ to PGE₂ in downstream of cyclooxygenase-2 (COX-2). Recent studies have obtained in vitro evidence that PGE₂ participates in carcinogenesis, angiogenesis, and induction of matrix metalloproteinase-9 (MMP-9), which plays a crucial role in cancer invasion. However, implications for mPGES-1 in thyroid carcinomas remain to be determined. To address this issue, we performed an immunohistochemical analysis for mPGES-1, COX-2 and MMP-9 in 20 papillary thyroid carcinoma (PTC) patients. mPGES-1 immunoreactivity was localized in the cytoplasm of carcinoma cells in 19 cases, with an intensity that tended to be distinct at the interface between the tumor and the surrounding non-neoplastic tissue. Staining was more intense in regions with papillary arrangement, while it was less intense in regions with trabecular or solid arrangement. In many cases, immunohistochemical localization of COX-2 and MMP-9 resemble that of mPGES-1. Taken together, our results suggest the involvement of mPGES-1 in proliferation and differentiation of PTC as well as local invasion of PTC.