基质金属蛋白酶-9、金属蛋白酶组织抑制因子-1、血管内皮生长因子和转化生长因子β-1在甲状腺乳头状癌和滤泡癌的表达及意义

目的 探讨基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制因子-1(TIMP-1)、血管内皮生长因子(VEGF)和转化生长因子β-1(TGFβ-1)表达与甲状腺乳头状癌和滤泡癌分化、浸润、转移的关系.方法 采用免疫组织化学EnVision法检测85例乳头状癌和59例滤泡癌中MMP-9、TIMP-1、VEGF和TGFβ-1的表达.结果 MMP-9、TIMP-1、VEGF、TGFβ-1表达于癌细胞的胞质,体现于阳性率和阳性强度两方面.乳头状癌在MMP-9、TIMP-1、VEGF和TGFβ-1的表达阳性率(83.5%、81.2%、90.6%和75.3%)和强度均低于或相近于滤泡癌(93.2%、86.4%、89.9%和78.0%).乳头状癌中有转移组的四种免疫学指标表达均高于无转移组;滤泡癌低分化型组在MMP-9、VEGF、TGFβ-1的表达均高于高分化型组,仅TIMP-1阳性率与阳性强度则显示相反表达.提示随两种癌分化程度的下降和出现转移MMP-9、TIMP-1、VEGF、TGFβ-1表达逐渐增高呈正相关关系,而且两种癌的VEGF、MMP-9表达均高于TIMP-1、TGFβ-1,后两者的阳件强度相对较低.结论 综合检测MMP-9、TIMP-1、VEGF和TGFβ-1四种免疫学指标,对探讨甲状腺乳头状癌和滤泡癌分化、浸润、转移和评估预后具有一定参考价值.     

MMP-2 but not MMP-9 associated with COX-2 and survival in gastric cancer

BACKGROUND AND AIM: Matrix metalloproteinases (MMPs) MMP-2 and MMP-9 can degrade type IV collagen of extracellular matrix and basal membranes. As cyclo-oxygenase-2 (COX-2) has been shown to activate MMPs, creating one of the COX-2-promoted pathways of tumour growth and metastasis, the prognostic role of MMP-2 and MMP-9 in gastric cancer was assessed and their association with COX-2 expression was evaluated. MATERIALS AND METHODS: Samples were collected from 342 consecutive patients operated on for gastric cancer, of which 315 were acceptable for MMP-2, MMP-9 and COX-2 immunohistochemistry. Specimens were stained with specific antibodies, evaluated and categorised by two interpreters, and then correlated with clinical data and survival. RESULTS: Epithelial MMP-2 immunoreactivity was associated with male sex, high stage, advanced penetration depth, non-curative surgery, high COX-2 expression and poor survival. Stromal MMP-2 expression correlated with high stage, intestinal type and non-curative surgery whereas MMP-9 correlated only with intestinal type. Stage, intent of surgery and COX-2 were independent prognostic factors. CONCLUSIONS: Epithelial MMP-2 expression in gastric cancer is associated with aggressive forms, COX-2 and poor survival, although MMP-2 was not an independent prognostic factor. In gastric cancer tumour growth is apparently induced by COX-2, and invasion is mediated by MMP-2.     

核仁素在甲状腺乳头状癌中表达的临床意义

目的 探讨核仁素（NCL）在甲状腺乳头状癌中的表达及临床意义。方法 采用免疫组织化学SP染色法检测60例正常甲状腺组织与甲状腺乳头状癌中NCL、趋化因子受体-7（CCR7）与基质金属蛋白酶-9（MMP-9）的表达,分析NCL、CCR7与MMP-9的表达与性别、年龄、肿瘤大小与
有无转移的关系以及核仁素与CCR7、MMP-9表达的相关性。结果 NCL在正常甲状腺及甲状腺乳头状癌中的总阳性率分别为0、 100%。NCL在伴随转移组癌组织中表达于细胞核、细胞质与细胞膜;NCL在无转移组癌组织中仅表达于细胞核,差异有统计学意义（P<0.05）。不同年龄、性别、
肿瘤大小的NCL表达率间的差异无统计学意义(P>0.05)。核仁素细胞核外阳性表达与CCR7与MMP-9的阳性表达呈正相关（P<0.01）。结论 NCL在甲状腺乳头状癌中表达,表达部位在转移与非转移组明显不同,且与CCR7、MMP-9表达有密切关系。核仁素可作为区别癌转移与非转移的标志。     

Expression of Jun activation domain-binding protein 1 and p27 (Kip1) in thyroid medullary carcinoma

AIMS: p27 is a prominent regulator of cell proliferation by universally inhibiting the cell cycle, while Jun activation domain-binding protein 1 (Jab1), a multifunctional cell signaling protein, contributes to carcinoma progression by degrading p27. In this study, we investigated the expression of these proteins in medullary thyroid carcinoma. METHODS: We immunohistochemically examined Jab1 and p27 expression in 64 medullary thyroid carcinomas. RESULTS: Of the 64 cases examined, decreased p27 expression was observed in 38 cases (59.4%). The p27 expression level was inversely linked to tumour size as well as plasma calcitonin level. Jab1 expression level was generally high, and 46 cases (71.9%) were classified as overexpressing Jab1. The incidence was higher than those in papillary and follicular carcinomas, which were previously reported. Jab1 expression level was inversely linked to that of p27, and all five cases with only cytoplasmic but not nuclear staining of p27 overexpressed Jab1. CONCLUSIONS: These findings suggest that (1) decrease in p27 expression may contribute to local tumour growth; (2) Jab1 expression is related to the progression of medullary carcinoma by decreasing the amount of p27 in the cell and accelerating its degradation; and (3) Jab1 may play a more vital role in the pathogenesis of medullary carcinoma than papillary and follicular carcinomas.     

Expression of matrix metalloproteinases MMP-1, MMP-11 and MMP-19 is correlated with the WHO-grading of human malignant gliomas

Glioblastomas (GBM) are the most prevalent type of malignant primary brain tumor in adults. They may manifest de novo or develop from low-grade astrocytomas (LGA) or anaplastic astrocytomas. They are characterized by an aggressive local growth pattern and a marked degree of invasiveness, resulting in poor prognosis. Tumor progression is facilitated by an increased activity of proteolytic enzymes such as matrix metalloproteinases (MMPs). Elevated levels of several MMPs were found in glioblastomas compared to LGA and normal brain (NB). However, data for some MMPs, like MMP-1, are controversially discussed and other MMPs like MMP-11 and MMP-19 have as yet not been analysed in detail. We examined the expression of MMP-1, MMP-9, MMP-11 and MMP-19 in NB, LGA and GBM by semiquantitative RT-PCR, Western blotting and immunohistochemistry and found an enhanced expression of these MMPs in GBM compared to LGA or NB in signal strength and in the percentage of tumors displaying MMP expression. The transition from LGA to GBM was characterized by a shift of pro-MMP-11 to expression of the active enzyme. Therefore, MMP-1, MMP-11 and MMP-19 might be of importance for the development of high-grade astrocytic tumors and may be promising targets for therapy.     

The investigation of foxe1 variations in papillary thyroid carcinoma

Background: Recent reports indicated that incidence of thyroid carcinoma is increasing throughout the worldwide. The aim of our study was to determine a possible relationship between Forkhead box E1 (FOXE1) gene variants and histopathological features of papillary thyroid carcinoma. Methods: FOXE1 gene variations; rs894673, rs1867277 and rs3758249 were analyzed in 57 Papillary thyroid carcinoma patients and 51 age matched healthy control subjects. Restriction fragment length polymorphism (RFLP) technique was used to specifically detect the variations. Results: There was a significant difference in the distribution of rs894673 genotypes in Papillary thyroid carcinoma cases (P=0.01). AA genotype presence of rs1867277 was more significantly associated with several histopathological parameters such as focal and diffuse capsular invasion, lymphatic invasion, P3 with P4 tumor grade and surgical margins. AA genotype presence in rs1867277 variation was significantly associated with the classical variant which is subtype of papillary thyroid carcinoma. Furthermore, the presence of the allel A was found to be related with lymph node invasion risk by 2.46 fold, capsular invasion risk by 2.97 fold, and pT3 with pT4 pathological stage risk by 4.13 fold and the presence of allele A in rs1867277 was significantly associated with classic variants. The presence of allele A in rs1867277 was more significantly associated with several histopathological parameters in classic variant in papillary thyroid carcinoma cases such as, the presence of the A allele was found relationship with lymph node invasion risk by 2.0 fold, capsular invasion risk by 2.39 fold , and pT3 with pT4 pathological stage risk by 3.57 fold. In addition, AATT, AAAA and GATT haplotypes (rs1867277 and rs894673) were evaluated for association with papillary thyroid carcinoma cases. Our results indicate that the significant difference according to two-allele haplotype distribution between papillary thyroid carcinoma cases and control groups. Conclusion: Our findings suggest that FOXE1 variations generate a higher risk for poor histopatological features of papillary thyroid carcinoma.     

Differential expression of matrilysin-1 (MMP-7), 92 kD gelatinase (MMP-9), and metalloelastase (MMP-12) in oral verrucous and squamous cell cancer

Squamous cell carcinoma (SCC) of the oral cavity is a highly invasive tumour of stratified squamous epithelium that spreads through degradation of the basement membrane (BM) and extracellular matrix (ECM). There are currently no reliable tissue or serum markers to predict whether the tumour has metastasized at the time of diagnosis. Verrucous carcinoma (VC) of the oral cavity is a rare low-grade variant of oral SCC that penetrates into the subepithelial connective tissue. Many matrix metalloproteinases (MMPs), such as MMP-1, -2, -7, -9, -13, and -14, as well as integrin receptors have been implicated in cancer invasion. Integrin alphavbeta6 is induced in SCC and appears to be involved in up-regulation of MMP-9 expression by oral keratinocytes and promotion of their migration. The aim of this study was to investigate whether the pattern of MMP expression or that of alphavbeta6 integrin contributes to the differences in the biological behaviour of oral SCC and VC. The results show that the less aggressive nature of oral VC may be connected to its MMP expression profile. Typically, VCs were devoid of epithelial MMP-3, -7, -9, -12 and -13 expression, compared with SCCs. MMP-19 was expressed by epithelial keratinocytes in hyperproliferative areas of verrucous hyperplasia, VC, and SCC, but was absent in the invasive cancer cell nests of SCC. MMP-26 was expressed by hyperproliferative keratinocytes in VC as well as by invasive cancer cells in SCCs. MMP-10 was expressed widely in the epithelium of all SCC specimens. alphavbeta6 integrin expression was also detected in some cases of epithelial hyperplasia but was significantly more abundant in cancers at the invasive front. The absence of MMP-7, -9 and -12 from epithelial cells may serve as a good prognostic marker of non-invasive oral carcinoma. Blocking the activity of invasion-specific MMPs or alphavbeta6 integrin might offer novel therapeutic modalities in early-stage oral carcinoma.     

Immunohistochemical localisation of RET and p53 mutant protein of thyroid lesions in a North-Eastern Malaysian population and its prognostic implications

AIMS: To investigate RET and p53 expression in local thyroid lesions, in order to shed light on the pathogenesis of papillary carcinoma and explain the high prevalence of this condition among the nodular hyperplasia (multi-nodular goitre) cases. METHODS: Archival thyroid tissue was retrieved from Hospital Universiti Sains Malaysia (HUSM) Pathology Department files and studied by immunohistochemistry for RET and p53 mutant protein. Normal tissues from 74 cases served as controls. RESULTS: Fifty follicular adenoma, 66 nodular hyperplasia and 53 papillary carcinoma cases were studied. RET was expressed in 5.4% of normal thyroid tissue, 18% of follicular adenomas, 22.7% of nodular hyperplasia cases and 71.7% of papillary carcinomas. Its expression in papillary carcinoma was not associated with the coexistence of nodular hyperplasia lesions. p53 was expressed by 17% of papillary carcinomas. No association was found between p53 expression of nodular hyperplasia with or without co-existing papillary carcinoma. p53, rather than RET, was an excellent predictor of tumour lymph node metastasis and capsular invasion. p53 was also a significant prognosticator of survival outcome. CONCLUSIONS: RET expression is highly prevalent in local papillary carcinoma, indicating a significant role in the pathogenesis of this tumour, with no apparent role in tumour behaviour and survival outcome. p53 on the other hand appears to be a significant factor in the latter events. The two genes appear to act in two different pathways: the former being an initiator, and the later a propagator of papillary carcinoma.     

Expression of matrix metalloproteinase 7 is an unfavorable postoperative prognostic factor in cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts

Cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts (collectively referred to as the large bile ducts) is an intractable disease, and a papillary phenotype and well-differentiated histologic grade have been proposed as indicators of a favorable prognosis after surgical resection. In this study, we examined the significance of matrix metalloproteinases (MMPs) in cholangiocarcinoma with respect to clinicopathologic features. We subjected 66 surgically resected specimens of cholangiocarcinoma of the large bile ducts to clinicopathologic examination, including postoperative survival, papillary phenotype, and immunohistochemical expression of MMP-2,-7, -9, and membrane type 1 MMP (MT1-MP). Nonneoplastic biliary epithelium did not express these 4 MMPs, whereas cholangiocarcinoma frequently expressed MMP-2 (33.9%), -7 (75.8%), -9 (47.5%), and MT1-MMP (54.5%). In particular, conventional (nonpapillary) cholangiocarcinoma expressed MMP-7 and MT1-MMP more frequently than papillary cholangiocarcinoma. The expression of MMP-7 and MT1-MMP significantly correlated with the nonpapillary phenotype, poorly differentiated histologic grade, perineural invasion, and advanced TNM stage. In contrast, the expression of MMP-2 and -9 was not associated with any of the clinicopathologic features. Univariate analysis of disease-specific survival revealed that a papillary phenotype and expression of MMP-7 were prognostic factors of cholangiocarcinoma, in addition to TNM stage, poorly differentiated histologic grade, perineural invasion, and microscopic margin status. Multivariate analysis showed only TNM stage to be an independent prognostic factor. Expression of MMP-7 in cholangiocarcinoma is an unfavorable postoperative prognostic factor of cholangiocarcinoma arising from the large bile ducts. Underexpression of MMPs in papillary cholangiocarcinoma might be associated with a favorable prognosis.     

Expression of matrix metalloproteinases in benign and malignant follicular thyroid lesions

AIMS: To examine expression of matrix metalloproteinases (MMPs) and related proteins in follicular thyroid lesions (FTLs) and to determine their usefulness for differential diagnosis of FTLs, particularly between minimally invasive carcinoma and adenoma. METHODS AND RESULTS: Six widely invasive follicular carcinomas (WIFCs), 15 minimally invasive follicular carcinomas (MIFCs), 19 follicular adenomas (FAs) and 10 adenomatous goitres (AGs) were analysed immunohistochemically for MMP-1, MMP-2, MMP-7, MMP-9, membrane-type 1-MMP (MT1-MMP) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2). MMP-1 was positive in all FTLs. MMP-2 and MMP-7 were positive in more than 80% of WIFC and MIFC cases, whereas they were negative in all FA and AG cases except one MMP-2+ FA (P < 0.001). MMP-9 stained positive significantly more in MIFC than FA or AG cases (P < 0.05, respectively). The positivity of MT1-MMP and TIMP-2 was different among some of the FTLs, but with no significant difference between MIFC and FA cases. In-situ hybridization of MMP-2 and MMP-7 mRNA in selected cases demonstrated the expression of these enzymes in the tumour cells as well as in some stromal cells. CONCLUSIONS: Our results confirm MMP expression mainly in malignant FTLs and suggest that MMP-2 and MMP-7 may be useful markers to distinguish MIFC from FA.     

Expression and role of matrix metalloproteinases MMP-2 and MMP-9 in human spinal column tumors

Matrix metalloproteinases (MMPs) have been implicated in the process of tumor invasion and metastasis formation. Thus, we determined the expression of MMPs in various primary and metastatic spinal tumors in order to assess the role of these enzymes in spinal invasion. MMP expression was examined by immuno-histochemical localization, and quantitative evaluation of MMP protein content was determined by enzyme-linked immunosorbant assay (ELISA) and Western blotting. MMP enzyme activity was determined by gelatin zymography. Lung carcinomas and melanomas metastatic to the spine were shown to have higher levels of MMP-9 activity than those of breast, thyroid, renal metastases and primary spinal tumors. Immunohistochemical analysis revealed similar difference in expression of MMP-9 in tissue samples. When the tissue samples were subjected to gelatin zymography for examination of MMP-2 and MMP-9 activity and to ELISA and Western blotting for quantitative estimation of protein content, the most striking results were obtained for lung carcinomas and melanomas relative to the other tumors. Lung carcinomas and melanomas metastatic to the spine had considerably higher levels of MMP-9 activity than those of primary spinal tumor or breast, thyroid, and renal carcinoma metastases. Within the metastatic tumor category, neoplasms that are known to be associated with the shortest overall survival rates and most aggressive behavior, such as lung carcinomas and melanomas, had the highest levels of MMP-2 and MMP-9 activity compared to those less aggressive metastatic tumors such as breast, renal cell, and thyroid carcinomas. Our results suggest that MMPs may contribute to the metastases to the spinal column, and overexpression of these enzymes may correlate with enhanced invasive properties of both primary and metastatic spinal tumors.© Kluwer Academic Publishers 1998     

Expression of MMP-2 is associated with progression and lymph node metastasis of gastric carcinoma

AIMS: One important step in tumour invasion is the penetration of the basement membrane. Matrix metalloproteinases (MMPs) play a key role in the migration of normal and malignant cells through the basement membrane. The aim of this study was to investigate correlations between matrix metalloproteinase 2 (MMP-2) immunoreactivity and currently used classification systems and possible relationships between lymph node metastasis and MMP-2 expression. METHODS AND RESULTS: This prospective study analysed specimens obtained from 114 gastric cancer patients (mean age 64 years; range 33-86 years) who underwent gastrectomy with extended lymphadenectomy. All specimens were categorized according to UICC classification, WHO classification, tumour differentiation, Laurén classification, Ming classification and Goseki classification. Formalin-fixed paraffin-embedded tumour specimens were stained using an avidin-biotin complex peroxidase assay. MMP-2 expression in the tumour epithelium was studied by immunohistochemistry with semiquantitative (score 0-3) evaluation. The MMP-2 staining pattern was positive (score 1-3) in 93 (81.6%) specimens and negative (score 0) in 21 (18.4%) samples. No significant correlations were found between MMP-2 expression and other variables such as age, tumour differentiation, WHO, Lauren, Goseki, and Ming classifications. In contrast, the intensity of MMP-2 staining in tumour cells correlated significantly with depth of tumour infiltration (T-stage), lymph node metastasis (N-stage), distant metastasis (M-stage), and UICC stage. CONCLUSIONS: Expression of MMP-2 is strongly associated with tumour progression and lymph node metastasis in gastric cancer. Therefore MMP-2 staining may be clinically useful as predictor of tumour progression, especially for lymph node metastasis.     

Protein expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinase 1 and 2 in papillary thyroid carcinomas

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play an important role in tumor invasion and metastasis. There have been only a few studies on the protein expression of MMPs and TIMPs in thyroid carcinomas. Therefore, we investigated the protein expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 in 86 papillary thyroid carcinomas using immunohistochemistry, semiquantitative scoring morphometry of immunohistochemistry, gelatin zymography, and western blotting. We also examined the correlations between the immunohistochemical scores and several clinicopathological parameters. The immunoreactivities of MMP-2, MMP-9, TIMP-1, and TIMP-2 were largely located in the tumor cells or non-tumor follicular cells and to a much lesser extent in the fibroblasts and endothelial cells in the tumor and non-tumor regions. Compared with non-tumor regions, these four proteins tended to be overexpressed in the tumor cells; the overexpression was found in 64 of 86 (74%), 80 of 86 (93%), 79 of 86 (92%), and 64 of 86 (74%) cases for MMP-2, MMP-9, TIMP-1, and TIMP-2, respectively. Gelatin zymography showed distinct bands of MMP-2 and MMP-9 in tumor extracts but vague bands in non-tumor extracts. Western blotting revealed the specific bands of MMP-2 and MMP-9 in both tumor and non-tumor extracts. Morphometric scoring revealed that high expression of these proteins significantly correlated with large tumor size, presence of lymph node metastasis, high clinical stage, high intrathyroidal invasion, and high vascular invasion. These data suggest that MMP-2, MMP-9, TIMP-1, and TIMP-2 proteins and activities are increased in tumors cells of papillary thyroid carcinomas and that they play an important role in the invasion and metastasis of papillary thyroid carcinomas.     

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.     

Raf-1 Kinase Inhibitory Protein Expression in Thyroid Carcinomas

Raf-1 kinase inhibitory protein (RKIP) has been implicated in several fundamental signal transduction pathways that control cellular growth, differentiation, apoptosis and migration. RKIP is reduced in a variety of human carcinomas, but RKIP expression in thyroid carcinomas has not been analyzed at the protein level. In this study, we examined the immunohistochemical expression of RKIP in various subtypes of thyroid carcinoma. Immunostaining for RKIP was performed on 104 cases of primary thyroid carcinoma (40 papillary, 29 follicular, 11 medullary, 11 poorly differentiated, and 13 anaplastic carcinomas) and 26 cases of nodal metastatic tumor (17 papillary, 4 medullary, and 5 anaplastic carcinomas). Normal thyroid tissue and all cases of follicular, papillary, and medullary carcinomas showed uniform, strong cytoplasmic immunoreactivity for RKIP. With the exception of one case, poorly differentiated carcinomas also revealed strong RKIP expression. In contrast, RKIP expression was completely absent in all anaplastic carcinomas. The transition zone from the differentiated carcinoma component (strong RKIP expression) to the anaplastic carcinoma component (no RKIP expression) demonstrated a completely opposite pattern of RKIP immunoreactivity. This reduction of RKIP expression in anaplastic carcinoma was statistically significant (P?<?0.0001). Additionally, RKIP expression of nodal metastatic tumors corresponded with that of primary tumors: metastatic papillary and medullary carcinomas showed uniform, strong cytoplasmic RKIP immunoreactivity, in contrast, in metastatic anaplastic carcinomas, RKIP expression was completely absent. RKIP expression is significantly reduced in anaplastic thyroid carcinoma as compared to other subtypes of thyroid carcinoma. Further studies are necessary to elucidate the precise mechanism of RKIP action in anaplastic thyroid carcinoma.     

TBX2在甲状腺癌组织中的表达及其临床意义

目的:检测TBX2在甲状腺癌组织中的表达,探讨其临床意义。方法:应用RT-PCR方法检测TBX2在9例正常甲状腺、13例甲状腺腺瘤及67例甲状腺癌组织(其中甲状腺乳头状癌28例,甲状腺滤泡癌23例,甲状腺髓样癌14例,甲状腺未分化癌2例)中的表达。结果:TBX2mRNA在甲状腺癌组织中的阳性表达(阳性表达56例,占83.6%)明显高于其在正常甲状腺(阳性表达3例,占33.3%)及甲状腺腺瘤组织(阳性表达6例,占46.2%)中的阳性表达(P<0.05),差异有显著性;TBX2mRNA在甲状腺乳头状癌、甲状腺滤泡癌及甲状腺髓样癌(甲状腺未分化癌例数太少,无统计学意义)组织中的阳性表达强度(相对系数)分别为1.776±0.382、2.627±0.532、2.937±0.481;P<0.05,差异具有显著性。TBX2mRNA在甲状腺癌组织中的阳性表达强度与甲状腺癌组织的分化程度及组织学分型有关。结论:TBX2可能是甲状腺癌发生、发展的促进因子,并有可能成为甲状腺癌临床诊断及预后评估的又一重要参考指标。     

Expression of MMP-10, MMP-21, MMP-26, and MMP-28 in Merkel cell carcinoma

Merkel cell carcinoma (MCC) is an aggressive cutaneous tumor with poor outcome and increasing incidence. We examined by immunohistochemistry the expression of three novel matrix metalloproteinases (MMPs)—MMP-21, MMP-26, and MMP-28—in 44 primary MCC tumors and six lymph node metastases while MMP-10 served as a positive control. Their mRNA expression was also studied in the UISO MCC cell line basally and after various stimulations using quantitative real-time PCR. MMP-28 was observed in tumor cells of 15/44 samples especially in tumors <2 cm in diameter (p = 0.015) while 21/44 specimens showed MMP-28 in the tumor stroma. Expression of MMP-21 was demonstrated in tumor cells of 13/43 samples. MMP-26, instead, was positive in stromal cells (17/44) and its expression associated with tumors ≥2 cm in diameter (p = 0.006). Stromal expression of MMP-10 was the most frequent finding of the studied samples (31/44), but MMP-10 was detected also in tumor cells (17/44). Most of the metastatic lymph nodes expressed MMP-10 and MMP-26. MMP-10, MMP-21, and MMP-28 mRNAs were basally expressed by the UISO cells, and the corresponding proteins were detectable by immunostaining of cultured cells. IFN-α and TNF-α downregulated MMP-21 and MMP-28 expression. Our results suggest that novel MMPs may have a role in MCC pathogenesis: especially that MMP-26 expression in stroma is associated with larger tumors with poor prognosis. Expression of MMP-21 and MMP-28 seems to associate with the tumors of lesser malignant potential. We also confirm the previous finding on the role of MMP-10 in MCC pathogenesis.     

Expression of MMP-2 and -9 in short-term cultures of meningioma: influence of histological subtype

Matrix metalloproteinases (MMPs) belong to a super family of endopeptidases which have been implicated as crucial mediators of angiogenesis and tumour invasion in brain tumours. This study was undertaken in an attempt to establish the relationship between 2 specific MMPs and the main classical subtypes of meningioma. We examined the expression of MMP-2 and -9 (gelatinase-A and -B respectively), by gelatin zymography, in a series of 18 cell cultures derived from human meningiomas of a range of histological subtypes and grades of malignancy, including 7 meningothelial, 6 transitional, 2 fibroblastic and 3 atypical meningiomas. Our findings indicate that generally, the meningothelial subtype, had the weakest expression, the transitional subtype had an intermediate expression whereas the fibroblastic subtype had the strongest expression of both MMP-2 and -9. There was no correlation between other clinicopathological features (age, sex, site of tumour) and the level of MMP-2 and -9 expression. Although, the number of samples in this study is limited, these findings suggest that there may be a trend for association between the expression of these 2 MMPs and the main classical histological subtypes of meningioma.