Pancreatic solid pseudopapillary neoplasm

Pancreatic solid pseudopapillary neoplasm (SPN) is a rare low grade malignant tumour. Distinguishing this entity from other pancreatic neoplasms is critical for therapeutic decision making and prognostication. It predominantly affects young female patients <40 years of age, with excellent clinical outcome following surgical removal. The gold standard diagnostic test is cytopathological or histopathological assessment of fine needle aspirate. There are two main difficulties with this. First, SPN can present with morphological and immunohistochemical appearances that can closely mimic other pancreatic tumours, in particular, pancreatic neuroendocrine tumour (NET). Second, the amount of diagnostic material from fine needle aspiration can be limited. Here, we present a cytopathological case with both challenges during the pre-operative investigation of SPN. The case exemplifies the importance of combining morphological features with a targeted panel of immunohistochemistry to arrive at the diagnosis.     

电针耳穴对年龄相关性听力损失豚鼠听觉中枢β－catenin表达的影响

目的：探讨电针耳穴对D －半乳糖所致的年龄相关性听力损失豚鼠模型听觉中枢β－链蛋白（β－catenin）表达的影响。方法取3月龄豚鼠30只,随机分成三组：D －半乳糖模型组、D －半乳糖＋电针组和对照组,每组各10只;18月龄豚鼠10只作为自然老化组。D－半乳糖模型组给予D －半乳糖（300 mg · kg －1· d－1）颈背部皮下注射,每天1次,连续6周;对照组给予等量生理盐水注射相同部位、相同频次、持续相同时间;D －半乳糖＋电针组给予相同剂量的D －半乳糖颈背部皮下注射,30 min后给予电针听宫穴和翳风穴治疗15分钟,每日1次,共6周。自然老化组豚鼠常规饲养。上述实验结束后采用蛋白质印迹（Western blot）方法检测四组豚鼠下丘和听皮层β－catenin蛋白的表达变化。结果①与对照组相比,D－半乳糖模型组和自然老化组豚鼠下丘β－catenin蛋白表达量下降;与D－半乳糖模型组相比,D －半乳糖＋电针组下丘β－catenin蛋白表达量增加;②D －半乳糖模型和自然老化组豚鼠听皮层β－catenin蛋白表达量下降,D－半乳糖＋电针组其表达量增加。结论β－catenin蛋白可能通过Wnt／β－catenin信号通路,调控细胞生长、分化及凋亡,参与下丘和听皮层的老化过程;电针听宫穴和翳风穴可能通过增加下丘和听皮层β－catenin蛋白表达,经Wnt／β－catenin信号通路延缓豚鼠年龄相关性听力损失的发生。     

Mutations of the APC,beta-catenin,and axin 1 genes and cytoplasmic accumulation of beta-catenin in oral squamous cell carcinoma

Purpose: The Wnt pathway is involved in carcinogenesis and three regulatory genes of the Wnt pathway, APC, beta-catenin and Axin are mutated in some primary human cancers. Mutations in these genes can impair the down regulation of beta-catenin, which results in the stabilization of beta-catenin, accumulation of free beta-catenin and subsequent activation of the Wnt pathway. To clarify the genetic alterations of components of the Wnt pathway in oral squamous cell carcinoma (SCC), we examined mutations in the APC, beta-catenin and Axin genes and subcellular localization of beta-catenin. Methods: 20 oral SCC tissues and four cell lines derived from oral SCC were used. Mutational analysis was performed by a single-strand conformation polymorphism (SSCP) method and direct sequecing analysis. The samples were also examined by immunohistochemical staining and immunoblot analysis. Results: In 3 of 4 cell lines, mutations were observed in the APC and Axin1 genes without amino acid substitutions. In a clinical sample, a mutation in the Axin1 gene was detected; a T insertion at codon 250 resulted in the formation of a stop codon at codon 259. In addition, cytoplasmic accumulation of beta-catenin was observed in 3 (75%) of 4 cell lines and 18 (90%) of 20 cancer tissue samples. Conclusion: The Axin1 gene may be one of the mutational target in oral SCC. In addition, the cytoplasmic accumulation of beta-catenin is a common characteristic of oral SCC, but is not closely associated with mutational alterations in the APC, beta-catenin and Axin1 genes.     

Gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC): An immunohistochemistry study of 13 microsatellite stable cases

BackgroundMixed adenoneuroendocrine carcinoma (MANEC) is currently included in the category of neuroendocrine carcinomas but the therapeutically management is not yet defined.AimsTo present the immunohistochemical (IHC) features of the epithelial mesenchymal transition (EMT) of MANEC.Materials and methodsThe clinicopathological features of 13 consecutive cases of MANEC (6 gastric and 7 colorectal) were correlated with the IHC expression of the biomarkers E-cadherin, β-catenin, N-cadherin, vimentin, maspin, CD44 and S100. In all of the cases open surgery was performed.ResultsAll of the cases showed microsatellite stable status, expressed E-cadherin and membrane β-catenin in both components (neuroendocrine and adenocarcinoma) and were negative for N-cadherin, vimentin and S-100. The colorectal MANECs were negative for maspin. In gastric MANECs, maspin showed cytoplasm positivity in the neuroendocrine component and nuclear translocation in the adenocarcinoma cells. CD44 was positive in all of the cases, in both components. No tumor buddings were identified. Three of the 13 patients survived for at least 32 months, all of them showing lymphatic emboli but not lymph node metastases. Pure neuroendocrine lymph node metastases were seen in only four of the cases: one from stomach, two of the ascending colon and two cases of the upper rectum.ConclusionsGastrointestinal MANEC is a microsatellite stable tumor with nodular growth, which components might originate from a CD44-positive stem-like precursor cell. Lymph node status remains the most reliable prognostic parameter and agressivity seems to not be influenced by tumor budding degree or EMT-related features. The histologic aspect of metastatic component (neuroendocrine versus adenocarcinoma) should be included in the histopathological reports and might be used for establishing the proper-targeted therapy of MANEC.     

Clinical update on the management of pseudopapillary tumor of pancreas

Solid pseudopapillary neoplasm(SPN) is a rare tumor with malignant potential which is generally located in the tail of pancreas.The prevalence of SPN has increased with widespread use of cross sectional imaging.SPN is often misdiagnosed due to nonspecific clinical presentation and accurate diagnosis is essential for optimal management.Endoscopic ultrasound-FNA with immunohistochemistry can help in preoperative diagnosis.Surgery is the treatment of choice and a successful R0 resection is curative.Overall,SPN has a good prognosis.This review article focuses on pathogenesis,diagnosis and management of SPN.     

Beta-Cetnin和APC蛋白在卵巢上皮肿瘤中的表达及意义

目的:探讨卵巢良性上皮肿瘤,卵巢交界性上皮肿瘤及卵巢恶性上皮肿瘤中beta-Catenin和APC蛋白的表达及意义.方法:采用ABC免疫组织化学染色方法检测18例卵巢良性上皮肿瘤,13例卵巢交界性上皮肿瘤及17例卵巢恶性上皮肿瘤中beta-Catenin和肿瘤APC蛋白的表达.结果:卵巢恶性上皮肿瘤beta-Catenin异常表达率明显高于卵巢良性上皮肿瘤(P＜0.001),卵巢交界性上皮肿瘤beta Catenin异常表达率亦明显高于卵巢良性上皮肿瘤(P＜0.01);APC蛋白在卵巢良性上皮肿瘤的表达明显强于卵巢恶性上皮肿瘤,两者具有显著性差异(P＜0.05);卵巢上皮肿瘤中beta-Catenin和APC蛋白之间存在负相关,且具有统计学意义(r=-0.352,P＜0.05).结论:beta-Catenin,APC蛋白在卵巢上皮肿瘤的发生,发展过程中起重要作用.     

AXIN1 and AXIN2 variants in gastrointestinal cancers

Mutations in the APC (adenomatous polyposis coli) gene, which encodes a multi-functional protein with a well-defined role in the canonical Wnt pathway, underlie familial adenomatous polypsosis, a rare, inherited form of colorectal cancer (CRC) and contribute to the majority of sporadic CRCs. However, not all sporadic and familial CRCs can be explained by mutations in APC or other genes with well-established roles in CRC. The AXIN1 and AXIN2 proteins function in the canonical Wnt pathway, and AXIN1/2 alterations have been proposed as key defects in some cancers. Here, we review AXIN1 and AXIN2 sequence alterations reported in gastrointestinal cancers, with the goal of vetting the evidence that some of the variants may have key functional roles in cancer development.     

Expressions of GSK-3beta, Beta-catenin and PPAR-gamma in medulloblastoma

Objective  To investigate the expressions of GSK-3beta, Beta-catenin and PPAR-gamma, and their relationship in medulloblastoma, and to explore their value in clinic application. Methods  Immunohistochemical staining with SP method was conducted to determine the expressions of GSK-3beta, Beta-catenin and PPAR-gamma in 48 cases of medulloblastoma and 10 normal cerebellar tissues. Results  The rate of abnormal expressions of beta-catenin and PPAR-gamma in MB was higher than that in normal. Conversely, GSK-3beta in MB was lower than that in the normal (P<0.05). Furthermore, in medulloblastoma, beta-catenin and GSK-3beta showed a negative correlation, PPAR-gamma and beta-catenin had a positive correlation. Conclusion  Abnormal expression of beta-catenin plays a crucial role in the development of medulloblastoma. Meanwhile, PPAR-gamma and GSK-3beta which are tightly related with beta-catenin are both involved in the genesis and development of medulloblastoma.      

Multiple parameters are involved in the effects of cadmium on prenatal hepatocytes

Cadmium, a toxic heavy metal, expresses its toxicity by affecting several cellular functions, such as enzyme activities, DNA repair systems, redox state of the cell and signal transduction. Although the liver is a known target organ, the mechanisms involved in cadmium toxicity are not yet clarified, especially during prenatal development. Here we consider the effects of cadmium on viability, proliferation, adhesion and defence mechanisms in primary adult and fetal rat hepatocytes. Fetal hepatocytes are less sensitive to cadmium toxicity, they appear to be unaffected or even stimulated by treatments that strongly inhibit DNA synthesis in adult cells. The behaviour of proteins involved in cell cycle regulation also differs from adult cells, according to the proliferative state. In addition, following Cd exposure, E-cadherin/beta-catenin complex disassembles in both cell types, with fetal cells being influenced at higher doses. The beta-catenin is not found in the nucleus, ruling out a direct role on DNA synthesis stimulation. Finally, metallothionein is more easily inducible in fetal hepatocytes, while Cd intracellular concentrations and HSP protein levels are not differentially affected. In conclusion, multiple cellular targets are affected by Cd in primary hepatocytes and the adverse effects of the metal are always better counteracted by fetal cells.