Association between the HLA-G molecule and lymph node metastasis in papillary thyroid cancer

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and can present as lymph node metastasis in 30 to 65% of cases when initially diagnosed. High frequency recurrence, distant metastasis and treatment resistance can be found in cases of PTC so early diagnosis and treatment are critical for improved prognosis and better survival rates. The characterization of new biomarkers has proved useful for the diagnosis and follow-up of these patients. HLA-G is a non-classical HLA class I molecule whose expression in cancer cells has been associated with tumor evasion of immune response. Therefore, the aim of this study was to investigate the HLA-G expression and its clinical significance in PTC. Paraffin-embedded thyroid biopsies of 70 PTC patients (40 of whom had presented with metastasis) were evaluated. HLA-G-staining was observed in tumor cells in PTC, and the HLA-G expression was significantly associated with an increased occurrence of lymph node metastasis (p = 0.0006) and capsular invasion (p = 0.02). This preliminary data shows the HLA-G expression in thyroid carcinoma specimens for the first time and suggests that this expression could impair efficient anti-tumor immunity in PTC. This would indicate that HLA-G could have an independent prognostic value in PTC, principally for tumor recurrence.     

Glyoxal Fixation and Its Relationship to Immunohistochemistry

Abstract

Glyoxal is a popular substitute for formalin and in many ways acts like it, although there are significant differences. When formulated correctly, glyoxal fixatives produce superior morphological detail in only 1-9 h, but crosslinking does not occur. Glyoxal has a unique reactivity with arginine, producing a cyclic imidazole in place of the highly charged guanidinium group, thus reducing eosinophilia in arginine-rich tissue elements. In the absence of crosslink-induced masking of epitopes, most antibodies work directly on glyoxal-fixed specimens without the need for antigen retrieval. The arginine reaction does cause loss of immunoreactivity in arginine-rich antigens, however. Fortunately, the imidazole is readily removed by a simple antigen retrieval process: pH 8.6 Tris HCl buffer for 10 min at 125°C. The conformational basis for needing antigen retrieval, and how it works on a molecular level is explained for both glyoxal and formalin fixation. (The J Histotechnol 29:65, 2006)

Submitted November 4, 2005; accepted with revisions March 15, 2006.     

Estrogen Activation of G-Protein–Coupled Estrogen Receptor 1 Regulates Phosphoinositide 3-Kinase and mTOR Signaling to Promote Liver Growth in Zebrafish and Proliferation of Human Hepatocytes

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Systems Biology Analyses Show Hyperactivation of Transforming Growth Factor-β and JNK Signaling Pathways in Esophageal Cancer

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Weaker ERG expression in patients with ERG-positive prostate cancer is associated with advanced disease and weaker androgen receptor expression: An Indian outlook

IntroductionGene fusion between TMPRSS2 and ERG has a causal role in prostate cancer initiation. However, studies evaluating its role clinically have shown conflicting results. We investigated simultaneously multiple aspects of ERG, namely, “presence” and “strength” of ERG expression and “correlation” of ERG with other common clinicopathological parameters.Materials and methodsFrom January 2012 to November 2013, the status of ERG, androgen receptor (AR), and p53 was prospectively determined by immunohistochemistry unselectively in all types of specimens positive for prostate cancer. “Strength” of expression was measured in terms of “intensity” as well as “percentage positivity,” with each parameter given a score from 0 to 3 based on fixed protocol, which was tested for interrater variability as well as test-retest reliability. Data were collected for age, Gleason score, prostate specific antigen levels, presence of perineural invasion and lymphovascular invasion, high-grade prostatic intraepithelial neoplasia, and cancer stage.ResultsIn total, 100 specimens were analyzed, and overall 51 patients had ERG-positive immunostaining. ERG-positive tumors had lower presence of high-grade prostatic intraepithelial neoplasia and p53 positivity, with no significant difference in prostate specific antigen levels, Gleason scores, and presence of lymphovascular invasion. Moreover, 54 patients had complete stage information, and the absolute number of patients with ERG positivity increased with increasing clinical stage. Among these, 30 patients were ERG positive, and ERG score had strong positive correlation with AR expression (Spearman correlation coefficient 0.677). However, median ERG scores showed a significant decline (consistent across percentage positivity and intensity) in patients with stage 4 disease, and score≤2 had 88.2% specificity in identifying patient with stage 4 disease. Cohen׳s κ = 0.81, whereas intraclass correlation coefficient was 0.95, indicating substantial agreement and near-perfect reproducibility of scoring scheme for immunohistochemistry.ConclusionERG-positive tumors increase in proportion with increasing stage of disease, but strength of ERG expression in ERG-positive patients shows a significant decline, or “loss,” in patients with stage 4 disease. This may have potential therapeutic implications as ERG expression score showed strong positive correlation with AR expression score.     

卵巢上皮性癌组织及外周血中septin-9的表达情况

目的 探讨卵巢上皮性癌组织及外周血中septin-9蛋白水平检测的临床意义.方法 采用酶联免疫吸附分析法分别测定137例卵巢上皮性癌患者、12例卵巢交界性肿瘤患者、10例卵巢良性肿瘤患者、41例盆腔良性疾患病人和58例健康人外周血血浆中septin-9蛋白水平.采用免疫组织化学染色方法分别测定54例卵巢上皮性癌患者、8例卵巢交界性囊腺瘤患者和8例卵巢囊腺瘤患者肿瘤组织中septin-9蛋白表达水平.结果 卵巢上皮性癌患者和盆腔良性疾患患者血浆中的septin-9蛋白水平(OD450=0.35±0.09;0.36±0.09)显著高于健康对照组(OD450=0.31±0.12) (P=0.002,P=0.007).卵巢上皮性癌患者外周血中septin-9水平,有肿瘤家族史组高于否认肿瘤家族史组(P=0.040),发生远处转移组高于未发生远处转移组(P=0.025).血浆中的septin-9蛋白水平与不同临床病理分期、分化、淋巴转移差异无统计学意义.组织中septin-9阳性表达率,卵巢上皮性癌组织为59.3％(32/54),卵巢交界性肿瘤组织为50％(4/8),卵巢良性肿瘤组织为0(0/8),各组间比较差异有统计学意义(P=0.007).结论 卵巢上皮性癌患者外周血中septin-9蛋白水平显著高于健康人群,盆腔良性疾病组患者外周血中septin-9蛋白水平显著高于健康人群.Septin-9与卵巢上皮性癌远处转移密切相关.卵巢上皮性癌组织、卵巢交界性肿瘤组织中septin-9阳性表达率显著高于卵巢良性肿瘤组织.     

NO-releasing xanthine KMUP-1 bonded by simvastatin attenuates bleomycin-induced lung inflammation and delayed fibrosis

Background and purposePulmonary fibrosis (PF) is a progressing lung injury initiated by pulmonary inflammation (PI). Bleomycin (BLM) is the most common pathogenesis of PF through early PI and extensive extracellular matrix deposition. This study is aimed to determine whether NO-releasing KMUP-1 inhibits PI and PF, and if so, the benefits of KMUP-1S resulted from simvastatin (SIM)-bonding to KMUP-1.Experiment approachC57BL/6 male mice were intra-tracheally administered BLM (4 U/kg) at day 0. KMUP-1 (1–5 mg/kg), KMUP-1S (2.5 mg/kg), SIM (5 mg/kg), Plus (KMUP-1 2.5 mg/kg + SIM 2.5 mg/kg), and clarithromycin (CAM, 10 mg/kg) were orally and daily administered for 7 and 28 days, respectively, to mice, sacrificed at day-7 and day-28 to isolate the lung tissues, for examining the inflammatory and fibrotic signaling and measuring the cell population and MMP-2/MMP-9 activity in broncholaveolar lavage fluid (BAL).Key resultsKMUP-1 and KUP-1S significantly decreased neutrophil counts in BAL fluid. Fibroblastic foci were histologically assessed by H&E and Masson's trichrome stain and treated with KMUP-1 and references. Lung tissues were determined the contents of collagen and the expressions of TGF-β, α-SMA, HMGB1, CTGF, eNOS, p-eNOS, RhoA, Smad3, p-Smad3, MMP-2 and MMP-9 by Western blotting analyses, respectively. These changes areregulated by NO/cGMP and inhibited by various treatments. KMUP-1 and KMUP-1S predominantly prevented HMGB1/MMP-2 expression at day-7 and reduced TGF-β/phosphorylated Smad3 and CTGF at day-28.Conclusions and implicationsKMUP-1 and KMUP-S restore eNOS, inhibit iNOS/ROCKII/MMP-2/MMP-9, attenuate histologic collagen disposition and reduce BALF inflammatory cells, potentially useful for the treatment of BLM-lung PF.