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.     

MicroRNA Expression Profiles in Thyroid Tumors

MicroRNAs (miRNAs) constitute a recently identified class of small endogenous noncoding RNAs that act as negative regulators of the protein-coding gene expression and may impact cell differentiation, proliferation and survival, i.e., all fundamental cellular processes implicated in carcinogenesis. miRNA expression is deregulated in many types of human cancers, including thyroid cancer. The purpose of this review is to summarize the existing findings of miRNA deregulation in thyroid tumors and its potential role in thyroid cancer biology and molecular diagnostics.     

A Comparison of Lectin Binding to Frozen,Formalin Fixed Paraffin Embedded,and Acid Decalcified Paraffin Embedded Tissues

Abstract

A comparison was made between lectin binding to frozen, formalin fixed paraffin wax embedded, and to formic acid treated, paraffin wax embedded tissues, using three lectins UEA I, PNA, SBA. The binding to various rat tissues was assessed with a multiple layer immunoperoxidase staining method. Except for an increase in binding to some tissues, there was little difference between the acid treated and non-acid treated formalin fixed, paraffin embedded tissues. With several tissues, differences between frozen and paraffin embedded specimens suggested that care should be exercised in the choice of tissue processing if lectin histochemistry is to be undertaken. (The J Histotechnol 11:223, 1988.)     

胃癌与癌旁组织miRNA差异表达谱的研究

目的 研究胃癌中表达失调的miRNA及其生物学功能,从而进一步阐明miRNA在胃癌发生中的分子机制.方法 将总RNA加ploy(A)尾后进行反转录PCR扩增特异miRNA,使用QuantityOne软件进行定量分析,计算每对样本胃癌与癌旁组织比值(T/N Ratio),使用SAM软件进行统计分析.MTT法检测miR-21和miR-17-5p对胃癌细胞系生长的影响.结果 在8对胃癌及癌旁组织样本中对237个miRNA进行了表达谱分析.对于检测到表达的161个miRNA,使用SAM软件进行统计分析,确认22个在胃癌中表达上调,2个在胃癌中表达下调(FDR=0.0963).进一步通过生长抑制试验证实在胃癌组织中表达异常增高的miR-21和miR-17-5p对胃癌细胞的生长有明显的促进作用.结论 这些在胃癌中异常表达的miRNAs具有成为新一代胃癌标记物的潜力,能够为胃癌的精确诊断分型提供依据,同时针对这些靶点可以开发新的核酸治疗技术,通过抑制或增强其功能来达到治疗胃癌的目的.     

Galectin-3 Expression in Tumor Progression and Metastasis of Papillary Thyroid Carcinoma

Galectin-3 plays important roles in cell adhesion, cell proliferation, apoptosis, neoplastic transformation, and metastasis. Galectin-3 expression has been evaluated in various malignant neoplasms to determine its effectiveness in differential diagnosis from benign lesions and its effects on carcinogenesis. There are few and somewhat controversial results regarding its changes through cancer progression in thyroid malignancies. We studied the presence of galectin-3 expression immunohistochemically and its relation with tumor invasiveness and lymph node metastasis in 89 cases of papillary carcinoma of the thyroid. Galectin overexpression was less frequent in cases with lymph node metastases compared with cases without lymph node metastasis (P = 0.001). Metastatic foci in lymph nodes showed a lower degree of galectin-3 overexpression than their primary lesions (P = 0.001). Degree of galectin-3 overexpression was also lower in larger tumors (P = 0.009). Additionally, a decreased level of galectin-3 overexpression was observed at the invasive edges of the tumors (P = 0.001). Galectin-3 overexpression is more profound in early stages of papillary carcinoma, and its expression intensity decreases during tumor progression. This finding is consistent with roles for galectin-3 in cell adhesion to other tumor cells and the matrix.     

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.     

MicroRNA Expression Profiling Outperforms mRNA Expression Profiling in Formalin-fixed Paraffin-embedded Tissues

microRNAs (miRNAs) are ∼22nt RNAs that regulate target gene expression. Altered expression of miRNAs has been demonstrated in many different human cancers. Many studies using microarray technologies to characterize miRNA expression profiles have relied on fresh tissue to determine the miRNA signatures. In this study, we prepared total RNA from paired samples of formalin-fixed paraffin-embedded (FFPE) and fresh frozen malignant melanoma, and used that in microarray experiments to compare miRNA expression profiles between FFPE and fresh tissue with corresponding mRNA expression profiles from the same tissue sources. We demonstrate that miRNA expression profile from FFPE tissues closely resembles that from fresh tissues, and the correlation is significantly better than that for mRNA profiles from FFPE and fresh tissues. These results underscore the suitability of FFPE tissues as appropriate resources for molecular expression analyses and support the notion that miRNAs are more vigorous analytes for this purpose than mRNAs.     

Langerhans Cell Histiocytosis of the Lung and Thyroid, Co-Existing with Papillary Thyroid Cancer

A 24-year-old man presented to our center with a huge goiter compressing his airway. He had a previous diagnosis of Langerhans cell histiocytosis (LCH) of the lung. Core needle biopsy was consistent with histiocytosis. Thyroidectomy was performed. A very invasive mass was encountered at the time of surgery. Histopathology result was consistent with an invasive papillary cancer of thyroid co-occurring with LCH. Although association of LCH with different malignancies has been reported, co-existing invasive papillary thyroid cancer and LCH is a rare combination.     

Differential Expression of a Set of Genes in Follicular and Classic Variants of Papillary Thyroid Carcinoma

Fine-needle aspiration biopsy (FNA) is currently the best initial diagnostic test for evaluation of a thyroid nodule. FNA cytology cannot discriminate between benign and malignant thyroid nodules in up to 30% of thyroid nodules. Therefore, an adjunct to FNA is needed to clarify these lesions as benign or malignant. Using differential display-polymerase chain reaction method, the gene expression differences between follicular and classic variants of papillary thyroid carcinoma (PTC) and benign thyroid nodules were evaluated in a group of 42 patients. Computational gene function analyses via Cytoscape, FuncBASE, and GeneMANIA led us to a functional network of 17 genes in which a core sub-network of five genes coexists. Although the exact mechanisms underlying in thyroid cancer biogenesis are not currently known, our data suggest that the pattern of transformation from healthy cells to cancer cells of PTC is different in follicular variant than in classic variant.     

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.     

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.     

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.     

Different CXCR4 Expression According to Various Histologic Subtype of Papillary Thyroid Carcinoma

Functional chemokine (C-X-C motif) receptor 4 (CXCR4) is well known to be over-expressed in papillary thyroid carcinoma (PTC). The aim of this study was to evaluate whether or not the expression of CXCR4 is different by histological subtypes of PTC and to elucidate the relationship between the expression of CXCR4 and clinicopathologic factors. CXCR4 expression in 127 PTC samples was assessed using immunohistochemical staining. The expression of CXCR4 showed different patterns according to the histological subtype of PTC (p?<?0.001). A strong expression of CXCR4 was observed more frequently in the poorly differentiated region of PTC (81.0 %) than in classical PTC (50.0 %). Strong CXCR4 expression was less frequently shown in follicular variant (33.9 %) and in diffuse sclerosing variant (14.3 %) of PTC. CXCR4 expression showed a distinct pattern according to the histological subtype of PTC although not associated with other clinicopathological parameters.     

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。     

甲状腺切除术后应用甲状腺平面显像评估残余甲状腺:与治疗剂量131I扫描的对比

目的:我国常用^99mTc甲状腺扫描评估甲状腺癌术后残余甲状腺大小,本文拟对甲状腺扫描与治疗剂量的¹³¹I扫描进行比较分析。方法:148例（男51,女97）2年内就诊甲状腺癌术后病人入组,年龄（47.0±13.3）岁,2名核医学科医师独立、盲法阅片,采用5分法计分。统计学分析采用秩相关研究,相关系数采用t检验进一步比较。结果:69/148（46.6%）两种显像结果得分一致,79（53.4%）¹³¹I扫描得分高于甲扫。甲扫及¹³¹I扫描评分结果与甲状腺激素水平均相关（P<0.001）,且相关系数间甲扫与T₃、T₄相关程度更高（t₁=-1.933,P=0.028;t₂=-2.788,P=0.003）。结论:^99mTc甲状腺平面显像可作为术后残余甲状腺的评估方法,但¹³¹I扫描显示范围更大,两者与甲状腺激素水平均相关,但甲扫与其相关性可能更高。     

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.