PRAME immunostain expression in sebaceous lesions, cutaneous carcinomas and adnexal structures.

The use of immunostain for PRAME antigen is well established for cutaneous melanolocytic lesions. However, its staining in other cutaneous structures and lesions is under reported. This study assessed PRAME staining in a large cohort of normal skin tissue, sebaceous lesions, and cutaneous carcinomas to better delineate patterns of PRAME immunoreactivity. PRAME immunostaining was performed on sections of sebaceous lesions and tissue microarrays of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs). Normal cutaneous adnexal structures were assessed on the sections of sebaceous lesions. For sebaceous lesions and non-lesional sebaceous glands, PRAME immunostaining was assessed for mature, germinative and sebocytes independently. A total of 193 sebaceous lesions, 64 BCCs and 35 SCCs were stained for PRAME immunostain. Staining pattern was predominantly cytoplasmic in normal apocrine glands, germinative sebocytes of sebaceous glands, and hair germs (p<0.001). Lesional sebocytes did not show different staining compared to normal sebaceous glands (p>0.05). Rare nuclear staining was observed in the normal epidermis (0.6%) and junctional melanocytes (4.1%). BCC, SCC and sebaceous carcinoma all showed low levels of PRAME immunoreactivity with variable proportions of cases demonstrating nuclear staining (BCC 59.4%, SCC 37.1%, sebaceous carcinoma 5.3%). PRAME immunostaining is positive in germinative sebocytes, various cutaneous structures and carcinomas. Nuclear staining, identical to melanoma, was observed in normal epidermis, junctional melanocytes, BCCs, SCCs, and sebaceous carcinomas. The pattern of PRAME staining in the skin must be recognised to avoid pitfalls in interpretating PRAME immunostain.

The 2021 WHO Classification of Tumors of the Central Nervous System: a summary.

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.

cIMPACT-NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT-Utrecht meeting on future CNS tumor classification and grading.

cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to evaluate and make practical recommendations on recent advances in the field of CNS tumor classification, particularly in light of the rapid progress in molecular insights into these neoplasms. For Round 2 of its deliberations, cIMPACT-NOW Working Committee 3 was reconstituted and convened in Utrecht, The Netherlands, for a meeting designed to review putative new CNS tumor types in advance of any future World Health Organization meeting on CNS tumor classification. In preparatory activities for the meeting and at the actual meeting, a list of possible entities was assembled and each type and subtype debated. Working Committee 3 recommended that a substantial number of newly recognized types and subtypes should be considered for inclusion in future CNS tumor classifications. In addition, the group endorsed a number of principles-relating to classification categories, approaches to classification, nomenclature, and grading-that the group hopes will also inform the future classification of CNS neoplasms.

Eyelid tumours and pseudotumours in Hong Kong: a ten-year experience.

OBJECTIVE: To describe the clinicopathological characteristics of patients with eyelid tumours in Hong Kong. DESIGN: Retrospective case series. SETTING: A tertiary eye centre in Hong Kong. PATIENTS: A computerised retrieval system was used to identify all patients who underwent eyelid mass excisions with histological reports, encountered in the period 2000 to 2009, in a tertiary eye centre. The demographics (age, gender), clinical features (laterality, tumour topography), and the pathological diagnosis of each patient were documented. Descriptive statistical tabulation and analyses were performed on the data. RESULTS: In all, 198 patients were identified; all were Chinese. Their mean age was 54 years for benign lesions and 68 years for malignant ones. Women were more commonly affected. Benign tumourous lesions occurred more commonly on the upper (n=91; 54%) than lower eyelid (n=79; 47%), whereas malignant lesions more often affected the lower (n=17, 61%) than upper (n=11, 39%) eyelid. The distribution of left and right eye involvement was similar (103 vs 101, respectively). In six patients, there were bilateral benign lesion. Regarding benign masses, 45 (27%) were intradermal neavi, 38 (22%) were squamous papillomas, 25 (15%) were seborrhoeic keratosis lesions, 14 (8%) were epidermoid cysts, and 7 (4%) were compound naevi. Regarding malignant eyelid tumours, the most common was basal cell carcinomas (n=12, 43%), 5 (18%) were squamous cell carcinomas, 3 (11%) were actinic keratosis lesions, and 2 (7%) each were sebaceous gland carcinomas and melanomas. CONCLUSION: Benign lesions constituted the majority of these eyelid tumours. Among the malignant lesions, basal cell carcinoma was the commonest type, with lower lid involvement in majority. Sebaceous gland carcinoma is not rare, which is in contrast to Caucasian populations. The relative frequencies of the most common malignant tumours in Hong Kong differed substantially from those reported in other Asian studies.

An uncommon mimic of spontaneous subarachnoid haemorrhage.

We here presented a rare disease entity with a clinical presentation mimicking aneurysmal subarachnoid haemorrhage. A 43-year-old woman presented with a 1-week history of neck pain and dizziness. Computed tomography of brain showed communicating hydrocephalus and subarachnoid hyperintensity suspicious of previous subarachnoid haemorrhage. Investigations revealed no underlying vascular lesion and leptomeningeal biopsy showed diffuse melanocytosis. We go on to discuss the diagnostic features and clinical course of this entity.

Pseudoprogression of malignant glioma in Chinese patients receiving concomitant chemoradiotherapy.

OBJECTIVES: To investigate the frequency of pseudoprogression of glioblastoma in Chinese patients receiving concomitant chemoradiotherapy and investigate its association with pseudoprogression and tumour molecular marker O(6)-methylguanine-DNA methyltransferase promoter methylation status. DESIGN: Case series with internal comparisons. SETTING: University teaching hospital, Hong Kong. PATIENTS: Patients with glioblastoma treated with concomitant chemoradiotherapy during April 2005 to June 2010 were reviewed. Magnetic resonance imaging brain scans, pre- and post-concomitant chemoradiotherapy and 3-monthly thereafter were reviewed by an independent neuroradiologist according to Macdonald's criteria. Relevant patient information (clinical condition, performance score, development of new neurological deficits, use of steroids, and survival) was retrieved. For each patient, O(6)-methylguanine-DNA methyltransferase methylation status was investigated with genomic DNA from formalin-fixed or paraffin-embedded sections of tumour tissues by methylation-specific polymerase chain reaction. RESULTS: During the study period, 28 primary glioblastoma patients underwent concomitant chemoradiotherapy. The mean age of the patients was 48 (range, 16-71) years. Thirteen patients (13/28, 46%) developed early radiological progression of the tumour after completion of concomitant chemoradiotherapy, of whom five (39%) were subsequently found to have had pseudoprogression. Patients with pseudoprogression showed a trend towards longer survival (22 months in pseudoprogression vs 17 months in all others vs 11 months in those with genuine progression). Among the 27 patients tested for O(6)-methylguanine-DNA methyltransferase promoter status, 12 (44%) were methylated. Two (2/12, 17%) in the methylated group had pseudoprogression, while three (3/15, 20%) in the unmethylated group had pseudoprogression. CONCLUSIONS: Nearly half of all patients (46%) developed early radiological progression (within 3 months of completing concomitant chemoradiotherapy). Moreover, about one in three of such patients had pseudoprogression. Pseudoprogression is an important clinical condition to be aware of to prevent premature termination of an effective treatment.

Association of TCF7L2 and ADIPOQ with body mass index, waist-hip ratio, and systolic blood pressure in an endogamous ethnic group of India.

Despite the increasing burden of type 2 diabetes (T2D) and its established association with anthropometric and physiological traits as a risk factor, genetic studies focusing on the association of T2D-related genes with quantitative traits like body mass index (BMI), waist-hip ratio (WHR), and systolic blood pressure (SBP) are only a few for western populations and rare for Indian populations. The present study tested the association of TCF7L2, HHEX, KCNJ11, and ADIPOQ with BMI, SBP, and WHR in men and women of the Aggarwal population of India and found a differential association of TCF7L2 (rs7903146, rs4506565, and rs12256372) and ADIPOQ (rs2241766 and rs1501299) genes with increasing BMI, SBP, and WHR between the two sexes. We conclude that TCF7L2 and ADIPOQ together might play an important role in explaining these traits and to understand the biological and genetic mechanisms underlying T2D, and the role of other T2D genes must also be evaluated with these continuous traits.

Attribution of human papillomavirus types to cervical intraepithelial neoplasia and invasive cancers in Southern China.

The attribution of individual human papillomavirus (HPV) types to cervical neoplasia, especially intraepithelial lesions, varies ethnogeographically. Population-specific data are required for vaccine cost-effectiveness assessment and type replacement monitoring. HPV was detected from 2,790 Chinese women (444 invasive cervical cancers [ICC], 772 cervical intraepithelial neoplasia [CIN] grade 3, 805 CIN2 and 769 CIN1. The attribution of each HPV type found in multiple-type infections was approximated by the fractional contribution approach. Multiple-type infection was common and correlated inversely with lesion severity (54.7% for CIN1, 48.7% for CIN2, 46.2% for CIN3, 27.5% for ICC). Vaccine-covered high-risk types (HPV16/18) attributed to 59.5% of squamous cell carcinoma, 78.6% of adenocarcinoma, 35.9% of CIN3, 18.4% of CIN2 and 7.4% of CIN1. Distinct features compared to worldwide were a higher attribution of HPV52 and HPV58, and a much lower attribution of HPV45. Inclusion of HPV52 and HPV58 in future vaccines would provide the highest marginal increase in coverage with 11.7% for squamous cell carcinoma, 14.4% for CIN3, 22.6% for CIN2 and 17.7% for CIN1. The attribution of HPV types in southern China is different from elsewhere, which should be considered in prioritizing HPV types for vaccine and screening assay development.

Association of molecular marker O(6)Methylguanine DNA methyltransferase and concomitant chemoradiotherapy with survival in Southern Chinese glioblastoma patients.

OBJECTIVES: (1) To compare the survival of concomitant chemotherapy and radiotherapy with radiotherapy alone in Chinese patients with primary glioblastoma. (2) To determine the methylation status of O(6)Methylguanine DNA methyltransferase in Chinese primary glioblastoma, and to assess the prognostic value of O(6)Methylguanine DNA methyltransferase methylation status in such patients. DESIGN: Retrospective correlative analysis. SETTING: University teaching hospital, Hong Kong. PATIENTS: Patients diagnosed with histologically proven primary glioblastoma in the period of March 2005 to June 2007 were recruited. Genomic DNA was isolated from formalin-fixed and paraffin-embedded sections of glioblastoma tissues. Methylation-specific polymerase chain reaction for O(6)Methylguanine DNA methyltransferase was performed. Patients' information at presentation was collected (age, performance status, steroid use, extent of resection, complications, radiotherapy data, use of chemotherapy). Primary outcome was measured by overall survival while secondary outcome was measured by progression-free survival. Overall and progression-free survivals were estimated by the Kaplan-Meier technique. Outcomes were assessed for groups with and without concomitant chemoradiotherapy and for groups with and without O(6)Methylguanine DNA methyltransferase methylation. RESULTS: A total of 35 glioblastoma patients were recruited; 27 were male and 8 female. Their mean age was 50 years. In all, 17 received concomitant chemoradiotherapy, and 18 received radiotherapy only. Their median overall survival was 12 (range, 7-17) months and the median progression-free survival was 5 (range, 3-6) months. In the radiotherapy alone group, the median progression-free survival and overall survival was 4 (range, 3-5) months and 6 (range, 2-10) months, respectively. In the concomitant radiochemotherapy group, the median progression-free survival and overall survival was 6 (range, 2-10) months and 13 (range, 8-18) months, respectively. Fifteen (43%) of the tumour samples showed methylation of O(6)Methylguanine DNA methyltransferase. There was a trend towards overall longer survival in the group with methylated tumours compared to those with unmethylated tumours; respective values for median survival (ranges) were 17 (13-21) versus 10 (6-14) months (P=0.105). CONCLUSIONS: Our single-centre results indicated that Chinese glioblastoma patients who had received concomitant chemoradiotherapy showed a trend towards longer overall survival compared to those receiving radiotherapy alone. Approximately 43% of our Chinese glioblastoma samples showed methylation of O(6)Methylguanine DNA methyltransferase. O(6)Methylguanine DNA methyltransferase methylation may be a significant prognostic factor in Chinese glioblastoma patients.

Minichromosome maintenance proteins 2, 3 and 7 in medulloblastoma: overexpression and involvement in regulation of cell migration and invasion.

Minichromosome maintenance (MCM) proteins 2-7 are important in DNA replication licensing. Functional roles beyond licensing are speculated. In addition, significances in medulloblastoma (MB) remain unclear. In this study, we showed the frequent deregulation of MCM2 and MCM3 expression in 7 MB cell lines and 31 clinical samples. Moreover, DAOY and ONS76 and the clinical samples expressed elevated MCM7 transcripts with genomic gain of the gene. Immunopositivity restricted to tumor cells was found in 41, 37 and 53 out of 73 MB cases for MCM2, MCM3 and MCM7, respectively. High-MCM3 expression was associated with poor prognosis. Knockdowns of these MCMs significantly inhibited anchorage-dependent and -independent MB cell growth. The inhibition of MCM3 expression by small interfering RNA knockdown was related to G1 arrest with reduced cyclin A expression, whereas the MCM2- and MCM7-knocked-down cells arrested at G2/M with increased cyclin A expression. Interestingly, we demonstrated the links of these MCMs with cell migration and invasion using wound-healing and Transwell migration/invasion assays. Exogenous overexpression of MCM2, MCM3 and MCM7 increased anchorage-independent cell growth, and also cell migration and invasion capabilities in MB cells. The knockdown reduced the number of filopodial cells and the cells with intense stress fibers by blocking cdc42 and Rho activation. Taken together, deregulation of MCM2, MCM3 and MCM7 expression might be involved in MB tumorigenesis and we revealed undefined roles of these MCMs in control of MB cell migration and invasion.

Extraction techniques for polycyclic aromatic hydrocarbons in soils.

This paper aims to provide a review of the analytical extraction techniques for polycyclic aromatic hydrocarbons (PAHs) in soils. The extraction technologies described here include Soxhlet extraction, ultrasonic and mechanical agitation, accelerated solvent extraction, supercritical and subcritical fluid extraction, microwave-assisted extraction, solid phase extraction and microextraction, thermal desorption and flash pyrolysis, as well as fluidised-bed extraction. The influencing factors in the extraction of PAHs from soil such as temperature, type of solvent, soil moisture, and other soil characteristics are also discussed. The paper concludes with a review of the models used to describe the kinetics of PAH desorption from soils during solvent extraction.

Survey for the presence of BK, JC, KI, WU and Merkel cell polyomaviruses in human brain tissues.

BACKGROUND: Recently three previously unknown polyomaviruses (KI, WU and Merkel cell polyomaviruses) have been identified from human specimens. The spectrum of clinical manifestations and their tissue tropism are currently unknown. Since a member of this virus family, JC virus, is well-known for its capacity to establish latency in human brain tissue where reactivation in immunocompromised individuals can result in fatal progressive multifocal leukoencephalopathy, we sought to examine for the presence of all the five known human polyomaviruses in a series of human brain tissues. OBJECTIVES: To investigate the possibility of neuropersistence of the newly identified human polyomaviruses. STUDY DESIGN: Autopsy brain tissues were collected from 10 different brain regions of 30 individuals who died from diseases unrelated to viral infections. Nested PCR was used to assess the presence or absence of viral DNA. RESULTS: Ten samples collected from five individuals were found to harbour JCV DNA. In contrast, none of the 300 brain tissues examined showed positive results for BK, KI, WU or Merkel cell polyomavirus. CONCLUSION: The newly identified KI, WU and Merkel cell polyomaviruses either do not, or have a much lower neuropersistent potential compared to JCV.

Activation of GPR30 inhibits the growth of prostate cancer cells through sustained activation of Erk1/2, c-jun/c-fos-dependent upregulation of p21, and induction of G(2) cell-cycle arrest.

G-protein-coupled receptor-30 (GPR30) shows estrogen-binding affinity and mediates non-genomic signaling of estrogen to regulate cell growth. We here showed for the first time, in contrast to the reported promoting action of GPR30 on the growth of breast and ovarian cancer cells, that activation of GPR30 by the receptor-specific, non-estrogenic ligand G-1 inhibited the growth of androgen-dependent and androgen-independent prostate cancer (PCa) cells in vitro and PC-3 xenografts in vivo. However, G-1 elicited no growth or histological changes in the prostates of intact mice and did not inhibit growth in quiescent BPH-1, an immortalized benign prostatic epithelial cell line. Treatment of PC-3 cells with G-1 induced cell-cycle arrest at the G(2) phase and reduced the expression of G(2)-checkpoint regulators (cyclin-A2, cyclin-B1, cdc25c, and cdc2) and phosphorylation of their common transcriptional regulator NF-YA in PC-3 cells. With extensive use of siRNA-knockdown experiments and the MEK inhibitor PD98059 in this study, we dissected the mechanism underlying G-1-induced inhibition of PC-3 cell growth, which was mediated through GPR30, followed by sustained activation of Erk1/2 and a c-jun/c-fos-dependent upregulation of p21, resulting in the arrest of PC-3 growth at the G(2) phase. The discovery of this signaling pathway lays the foundation for future development of GPR30-based therapies for PCa.