Immunohistochemical study of ependymal neoplasms: histological subtypes and glial and epithelial characteristics

Summary An immunohistochemical study on ependymal tumours was performed in order to determine what relationships exist between histological subtypes and epithelial or glial characteristics. Thirty-eight ependymal tumours were examined with antibodies to cytokeratin (CK), epithelial membrane antigen (EMA), transthyretin (TTR) and glial fibrillary acidic protein (GFAP) using the avidin-biotin-complex technique. They included 23 ependymomas, 13 anaplastic ependymomas, and 2 myxopapillary ependymomas. Only 3 of the 23 ependymomas were positive with EMA but 19 reacted with GFAP. None of them were positive with CK. Six of the 13 anaplastic ependymomas were positive with EMA, 3 with CK and 10 with GFAP. Five of the 6 anaplastic ependymomas which had epithelial marker proteins were either negative or weakly positive for GFAP. The present study demonstrates that most benign ependymomas exhibit GFAP positivity while the anaplastic ones tend to suppress their glial nature in favour of epithelial differrentiation. However, ependymal tumours showed few characteristics of choroid plexus cells; only one of the examined cases was positive for TTR.     

Leptomeningeal transthyretin-type amyloidosis presenting as acute hydrocephalus and subarachnoid hemorrhage

We present a report of a 47-year-old woman with developmental delay who presented with subarachnoid hemorrhage and acute hydrocephalus. She did not have an aneurysm, but there was symmetric calcification and gadolinium-enhancement of the meninges within the Sylvian fissure. Biopsy and genetic testing confirmed transthyretin-type amyloidosis. It is important to consider such rare causes in atypical presentations of non-aneurysmal subarachnoid hemorrhage.     

Emerging therapies in transthyretin amyloidosis – a new wave of hope after years of stagnancy?

Transthyretin amyloidosis (ATTR) is a rare, yet underdiagnosed disease characterized by progressive impairment of neurologic and cardiac function due to deposition of misfolded transthyretin. Despite great efforts, such as the introduction of orthotopic liver transplant, the devastating prognosis for both variant and wild‐type ATTR patients remained unchanged over the last decades, mainly due to a lack of specific therapies. Fortunately, recent years saw the introduction of promising targeted therapies, which aim to interfere with the deposition of misfolded transthyretin (TTR) at various stages of the cascade underlying ATTR progression. These include TTR tetramer stabilizers (tafamidis, diflunisal, epigallocatechin‐3‐gallate), TTR silencers (inotersen, patisiran) and fibril disruptors (monoclonal antibodies, doxycycline and tauroursodeoxycholic acid). In the context of this review we explain their mechanisms of action, analyse their efficacy on neurologic and cardiac function based on all clinical trials conducted to date and discuss their clinical applicability. Eventually suggestions for future clinical research into the field are provided.     

甲状腺素运载蛋白时间分辨免疫荧光试剂盒的制备和效能评价

目的制备甲状腺素运载蛋白(transthyretin,TTR)的时间分辨免疫荧光(time-resolved fluoroimmunoassay,TRFIA)试剂盒并对其性能进行评价。方法将抗TTR的4H2单克隆抗体作为包被抗体包被至96孔板,用Eu^3+标记3E4单克隆抗体作为检测抗体,制备双抗体夹心TRFIA试剂盒,应用该试剂盒对42例川崎病(Kawasaki disease,KD)患儿及13名健康儿童的血清进行检测,以稀释回收率、准确度、精密度、稳定性等指标对试剂盒的效能进行评价。结果该研究制备的TTR TRFIA试剂盒与Western blot法同时检测42份KD临床样本和13份健康样本,两方法的结果符合率为100%,特异性强。试剂盒的最低检出浓度为0.05μg/ml,稀释回收率为88.00%~111.00%,分析内精密度为8.01%~9.17%,分析间精密度为8.88%~11.82%。稳定性实验表明该试剂盒可在4℃稳定保存6个月,37℃稳定保存7 d。结论该研究制备的TTR TRFIA试剂盒具有准确性高、方便快捷等优点,适用于大批量临床KD血清样品的TTR检测,为快速区分丙种球蛋白敏感型和无反应型的KD患儿提供了方法。     

转甲状腺蛋白在重度子痫前期及胎儿生长受限孕妇血清中的表达及意义

目的:探讨转甲状腺蛋白(TTR)与s PE及FGR发病的关系及意义。方法:选取2012年9月1日至2015年2月1日在首都医科大学附属北京潞河医院产检并住院分娩的单胎孕妇120例,将患者分为4组:FGR组、s PE组、s PE+FGR组和对照组(各30例)。ELISA法检测TTR浓度。比较4组患者的年龄、孕次、产次、孕周、母血清TTR浓度等指标。结果:4组患者的年龄、孕次、产次、孕周等比较,差异无统计学意义(P0.05)。FGR组、s PE组及s PE+FGR组的母血TTR浓度较对照组明显降低,差异有统计学意义(P0.01)。s PE组血清中TTR含量低于FGR组,差异有统计学意义(P0.01)。结论:TTR在s PE、FGR和s PE+FGR孕妇血清中表达下调,有望成为s PE及FGR发生的生物标志物。s PE合并FGR可能由s PE本身的病理变化引起,s PE与FGR有着共同的病理基础。     

Ontogenic changes in placental transthyretin

Objectives

Before secretion of fetal thyroid hormone at around 16 weeks gestation normal fetal development depends on a constant supply of maternal thyroid hormone (TH), particularly thyroxine (T₄). The detailed mechanisms of transplacental delivery of TH are still uncertain. The TH binding protein, transthyretin (TTR), is produced and secreted by placenta and may play a role in this process. The ontogeny of placental TTR is unknown. Our aim was to study changes in placental TTR in early and late pregnancy.

Study design

We collected placentas from surgically terminated pregnancies between 6 and 17 weeks gestation (n = 44) and from normal term (38-39 weeks) pregnancies following caesarean section (n = 5). Real time-PCR, western blotting and immunohistochemistry were used to determine TTR mRNA and protein levels.

Results

There were highly significant correlations between gestational age and TTR mRNA (r = 0.974; p < 0.0001) and between gestational age and TTR protein (r = 0.901; p < 0.001) levels between weeks 6 and 13 of gestation. TTR expression did not increase between 13 and 17 weeks and was not different at term. Good correlation was observed between TTR mRNA and TTR protein between individual placental samples (r = 0.916; p < 0.0001). A similar trend was observed using immunohistochemical staining of placental paraffin sections.

Conclusions

Our results demonstrate that TTR is expressed in the human placenta from at least 6 weeks gestation. Levels rise during the first trimester at a time when placental oxygen tensions are also rising. We hypothesise that TTR production and secretion by the placenta may facilitate transplacental delivery of TH to the fetus.     

Oxygen concentration regulates expression and uptake of transthyretin, a thyroxine binding protein, in JEG-3 choriocarcinoma cells

Maternal thyroid hormone is provided to the fetus before the onset of fetal thyroid function (at about 16 weeks) and is essential for normal neurologic development. Mechanisms of transport are uncertain but transthyretin (TTR), a thyroxine binding protein produced by the placenta may be involved. Placental oxygen concentrations in early pregnancy are low, about 1% early in the first trimester and rising to 8% over the next 12 weeks. This study investigated the regulation of TTR expression, secretion and uptake in JEG-3 placental cells cultured at different oxygen concentrations. TTR mRNA and protein expression and ¹²⁵I-TTR and Alexa-Fluor594-TTR uptake were significantly higher in cells cultured at 1% and 3% O₂, than at 8% O₂. This suggests that increased carrier mediated T₄ transport by placental TTR may be induced by the low oxygen environment of early pregnancy, a time when the fetus has its highest requirement for transport of maternal T₄.     

Ovarian cancer risk assessment: a tool for preoperative assessment

Objectives

The objective of this pilot study was to determine if the combination of CA 125, menopausal status and prealbumin can be used to accurately predict ovarian cancer in women with pelvic masses.

Study design

Preoperative serum CA 125, prealbumin and menopausal status were prospectively determined. Results were formulated into an ovarian cancer risk assessment (OCRA) score and compared with final surgical pathology.

Results

OCRA was studied in 130 women. No cancers were found in women with a score less than 200. For all cancers, an OCRA score ≥ 200 had a sensitivity of 96%, specificity of 95% and positive predictive value of 95%. When the OCRA score of ≥200 was evaluated for its ability to predict ovarian cancer, the sensitivity, specificity, and positive predictive value were 100%, 83%, and 78%, respectively.

Conclusions

In this pilot study, OCRA was able to predict which women with pelvic masses were more likely to have ovarian cancer. The scoring system easily applied clinically and may help facilitate appropriate referral of women to gynecologic oncologists for optimal care.