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Journal of clinical pathology [journal]
- Type-specific HPV prevalence in invasive cervical cancer in the UK prior to national HPV immunisation programme: baseline for monitoring the effects of immunisation. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Nov 19.
To establish the human papillomavirus (HPV) type-specific prevalence in cervical cancer and high-grade cervical lesions in the UK prior to the introduction of national HPV vaccination.Specimens of cervical cancer (n=1235) and cervical intraepithelial neoplasia (CIN)3 (n=2268) were tested for HPV genotypes in England, Scotland, Wales and Northern Ireland. Data were pooled and weighted estimates presented.Among cervical cancer cases, 95.8% were positive for at least one high-risk (HR) HPV type. Restricting to those with HR HPV, the proportion positive for HPV16 and/or HPV18 was similar across countries (weighted overall prevalence 83.0%). This proportion decreased with increasing age at diagnosis (p=0.0005). HPV31, HPV33, HPV45, HPV52 and/or HPV58 were detected in 16.1% of HR HPV-positive cervical cancers and there was no significant association with age for these types. For HR HPV-positive CIN3 cases, there was a similar age-specific pattern with the highest positivity of HPV16 and/or HPV18 in the youngest age group (77.2%). The proportion of HR HPV CIN3 cases positive for HPV31, HPV33, HPV45, HPV52 and/or HPV58 was 36.3% in those aged <30 years at diagnosis.The prevalence of HPV 16 and/or 18 was high in all UK countries and highest in those diagnosed at a younger age. The UK is well placed to monitor the impact of HPV vaccination on type-specific HPV prevalence in cervical disease.
- KIT genetic alterations in anorectal melanomas. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Nov 14.
Mucosal melanomas (MM) represent a heterogeneous tumour population that exhibits site-specific molecular profiles.In a multicentre retrospective study, we investigated KIT aberrations in primary anorectal (AR) melanomas compared with melanoma metastatic to the gastrointestinal (GI) tract.Primary AR MM (n=31) and GI metastatic melanoma (n=27) were studied for KIT mutations on exons 11, 13, 17 and 18 by high-resolution melting analysis, direct sequencing and c-KIT expression by immunohistochemistry. Selected cases were also investigated for increased KIT gene copy number by fluorescent in situ hybridisation.Functional KIT mutations were demonstrated in 11/31 (35.5%) of AR melanomas and in 1/26 (3.8%) of GI melanoma metastases (p=0.004). A significant difference emerged between primary and metastatic MM with regards to KIT-positive immunostaining (p=0.002). Immunohistochemical c-KIT protein overexpression did not correlate with KIT mutational status. Increased KIT copy number was demonstrated in 5/20 AR primary cases.The rate of functional mutations in KIT is significantly higher in AR MM than in GI metastatic melanoma. KIT protein overexpression does not correlate with KIT mutations and cannot be used for screening purposes. Recognising the molecular heterogeneity of MM helps to identify patients who require a different therapeutic approach.
- Endotoxin detection in end-stage kidney disease. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Nov 6.
Endotoxin detection assays are not validated for use in end-stage kidney disease (ESKD). We investigated the accuracy and precision of the kinetic turbidimetric Limulus amoebocyte lysate (LAL) assay to detect endotoxin in plasma from patients with ESKD. Optimisation of endotoxin recovery from plasma using the detergent Tween 80 was also explored.Plasma samples from 7 patients with ESKD and 7 healthy subjects were spiked with different concentrations of endotoxin. Repeated measurements for endotoxin at each level of spike were performed to assess the accuracy and precision of spike recovery. Endotoxin recovery in plasma samples diluted in Tween 80 and water was compared.Mean endotoxin spike recovery was 111.6% and 125.2% in ESKD and healthy subjects, respectively. There was no statistical difference in spike recovery between ESKD and healthy plasma. Precision of the LAL assay in plasma spiked with low (0.05 EU/mL) and high (0.5 EU/mL) concentration of endotoxin spikes was 24.1% and 8.9%, respectively. The use of Tween 80 as a diluent for plasma significantly improved spike recovery in ESKD plasma (100.1% vs 70.4%, p<0.001).The kinetic LAL turbidimetric assay is a valid tool for the detection of blood endotoxin in patients with ESKD, although in blood specimens with low-level endotoxemia (≤0.05 EU/mL) the assay may be less accurate and precise. Tween 80 can be used as a diluent to optimise recovery of endotoxin in ESKD plasma.
- Molecular pathology analyses of two fatal human infections of avian influenza A(H7N9) virus. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Nov 6.
To investigate the histopathological manifestations of two fatal cases of H7N9 influenza A virus infection.Pulmonary and hepatic specimens from two fatal cases of H7N9 influenza virus infection were examined using H&E staining. Additionally, in situ hybridisation was performed with probes (ViewRNA) targeting H7N9 RNA and IP-10, interleukin (IL)-6 mRNA. The distribution of surfactant protein A (SP-A), surfactant protein B (SP-B), CD3, CD4, CD8, CD68 and C4d were determined with immunohistochemistry. Apart from the typical diffuse alveolar damage and hyaline membrane observed in severe influenza infection, we detected H7N9 RNA and massive intrapulmonary production of IP-10 and IL-6 mRNA using in situ hybridisation. Hyperplasia of type II pneumocytes was observed by H&E staining and immunohistochemistry. Proliferating macrophages and clustered neutrophils in the infected lungs were observed, whereas T lymphocytes, especially CD4T helper cells, were markedly depleted. No obvious complement deposition was found in lung tissues. Our findings suggest that H7N9 influenza virus induced an immunological response towards overt pulmonary inflammation and systemic lymphopenia which led to intense alveolar damage and respiratory failure.
- Diffuse decidual leucocytoclastic necrosis and NK cell aggregates: two distinct features of miscarriage. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Nov 5.
Primary histopathology of miscarriage remains undetermined in the majority of cases. This study was conducted to determine histological characteristics pertinent to miscarriage.The study groups were composed of elective abortions (n=29) and miscarriages (n=45) comprised of chromosomally normal (n=15) and abnormal cases (n=30). Immunohistochemistry was done against CD3, CD8, TIA-1 and CD56.Two histological features-diffuse decidual leucocytoclastic necrosis (DDLN) and decidual natural killer cell aggregates (NKCA)-were relatively common in miscarriages. The frequencies of DDLN and NKCA were different between the groups (p<0.05 and p<0.05, respectively). DDLN was found in 13.8% (4/29) of elective abortions, while it was observed in 60.0% (9/15) and 23.3% (7/30) of chromosomally normal and abnormal miscarriages, respectively. DDLN was more frequent in chromosomally normal miscarriages than in elective abortions (p=0.004). NKCA was present in 13.8% (4/29) of elective abortions, while being found in 33.3% (5/15) and 43.3% (13/30) of chromosomally normal and abnormal miscarriages, respectively. NKCA was more frequent in chromosomally abnormal miscarriages than in elective abortions (p=0.020).The findings strongly suggest that defective placentation and abnormal maternal immune response are associated with miscarriage. DDLN and NKCA seem to have diagnostic values in the pathological evaluation of miscarriage.
- ERG expression in chondrogenic bone and soft tissue tumours. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Nov 5.
We studied ERG expression in a large series of chondrogenic bone and soft tissue tumours to assess the value of ERG as a possible marker of chondroid/cartilaginous differentiation.Formalin-fixed, paraffin-embedded whole sections from 111 bone and soft tissue tumours with chondroid differentiation or a morphology that may mimic cartilaginous differentiation were retrieved. Immunohistochemistry was performed using anti-ERG monoclonal antibody directed against the N terminus. Nuclear staining was scored as negative (<5%), 1+ (5%-25%), 2+ (26%-50%), 3+ (>51%).Nuclear ERG expression was seen in all cases of soft tissue chondroma (8), chondromyxoid fibroma (7), chondroblastic osteosarcoma (6) and clear cell chondrosarcoma (1). 10/12 conventional chondrosarcomas were also positive for ERG. In cases of dedifferentiated chondrosarcoma, the well-differentiated component was positive in 7/9 cases, while all dedifferentiated foci were negative. In cases of mesenchymal chondrosarcoma, the hyaline cartilage component was positive in 2/4 cases, whereas the primitive component in all cases was negative. Variable positivity was identified in extraskeletal myxoid chondrosarcomas (4/9), chondroblastomas (3/8) and mixed tumours/myoepitheliomas (2/11). Only 1/12 chordoma was positive for ERG (1+). Interestingly, 15/17 enchondromas were negative for ERG.In this study, we further characterise the expression of ERG in mesenchymal tumours and found relatively constant nuclear ERG expression in selected chondrogenic tumours including conventional chondrosarcoma, chondromyxoid fibroma, chondroblastic osteosarcoma and clear cell chondrosarcoma. We also show that ERG may be a helpful ancillary tool in certain select diagnostic scenarios and that awareness of ERG expression in tumours with cartilaginous differentiation is important.
- Ion Torrent next-generation sequencing for routine identification of clinically relevant mutations in colorectal cancer patients. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Nov 5.
To evaluate the accuracy, consumable cost and time around testing (TAT) of a next-generation sequencing (NGS) assay, the Ion Torrent AmpliSeq Colon and Lung Cancer Panel, as an alternative to Sanger sequencing to genotype KRAS, NRAS and BRAF in colorectal cancer patients.The Ion Torrent panel was first verified on cell lines and on control samples and then prospectively applied to routine specimens (n=114), with Sanger sequencing as reference.The Ion Torrent panel detected mutant alleles at the 5% level on cell lines and correctly classified all control tissues. The Ion Torrent assay was successfully carried out on most (95.6%) routine diagnostic samples. Of these, 12 (11%) harboured mutations in the BRAF gene and 47 (43%) in either of the two RAS genes, in two cases with a low abundance of RAS mutant allele which was missed by Sanger sequencing. The mean TAT, from sample receipt to reporting, was 10.4 (Sanger) and 13.0 (Ion Torrent) working days. The consumable cost for genotyping KRAS, NRAS and BRAF was €196 (Sanger) and €187 (Ion Torrent).Ion Torrent AmpliSeq Colon and Lung Cancer Panel sequencing is as robust as Sanger sequencing in routine diagnostics to select patients for anti-epidermal growth factor receptor (EGFR) therapy for metastatic colorectal cancer.
- Ultrastructural features of eosinophilic oesophagitis: impact of treatment on desmosomes. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Oct 30.
A growing body of evidence suggests a role for altered epithelial barrier function in the pathophysiology of eosinophilic oesophagitis (EoE), but few have described the epithelial structure during inflammation. The purpose of this study was to define ultrastructural features of active, inactive EoE and control subject's oesophageal epithelia.We prospectively enrolled patients undergoing diagnostic upper endoscopy for evaluation of EoE. Mucosal pinch biopsies were obtained from the distal oesophagus and processed for routine histology and electron microscopic assessment. Clinical features of enrolled subjects were analysed and subjects were divided into four groups: normal, gastroesophageal reflux disease (GERD), inactive EoE and active EoE. Representative photomicrographs of the basal and superficial epithelia were reviewed for abnormalities. Desmosomes were quantified on the surface of epithelia three to four prickle-cell layers above the basal layer.Twenty-nine paediatric cases (ages 2-18 years) were enrolled in the study. We observed a significant decrease in the number of desmosomes per cell (DPC) of subjects with active EoE compared with inactive EoE, GERD and normal epithelia. With respect to DPC, no significant differences were found between inactive EoE compared with GERD or normal subjects. Additional ultrastructural features observed included epithelial microplicae and evidence of eosinophil transmigration, degranulation, and sombrero formation.Consistent with clinical and molecular findings, our ultrastructural data provide support for an altered oesophageal barrier in paediatric cases with active EoE, which may improve following treatment.
- Validation of whole slide imaging in the primary diagnosis of gynaecological pathology in a University Hospital. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Oct 29.
Experience in the use of whole slide imaging (WSI) for primary diagnosis in pathology is very limited. We aimed to determine the accuracy of interpretation of WSI compared with conventional light microscopy (CLM) in the diagnosis of routine gynaecological biopsies.All gynaecological specimens (n=452) received over a 2-month period at the Department of Pathology of the Hospital Clinic of Barcelona were analysed blindly by two gynaecological pathologists, one using CLM and the other WSI. All slides were digitised in a Ventana iScan HT (Roche diagnostics) at 200×. All discrepant diagnoses were reviewed, and a final consensus diagnosis was established. The results were evaluated by weighted κ statistics for two observers.The level of interobserver agreement between WSI and CLM evaluations was almost perfect (κ value: 0.914; 95% CI 0.879 to 0.949) and increased during the study period: κ value 0.890; 95% CI 0.835 to 0.945 in the first period and 0.941; 95%; CI 0.899 to 0.983 in the second period. Major discrepancies (differences in clinical management or prognosis) were observed in 9 cases (2.0%). All discrepancies consisted of small lesions (8 high grade squamous intraepithelial lesions of the uterine cervix, one lymph node micrometastasis of an ovarian carcinoma) underdiagnosed or missed in the WSI or the CLM evaluation. Discrepancies with no or minor clinical relevance were identified in 3.8% of the biopsies. No discrepancy was related to the poor quality of the WSI image.Diagnosis of gynaecological specimens by WSI is accurate and may be introduced into routine diagnosis.
- KIR genotype distribution among symptomatic patients with and without Helicobacter pylori infection: is there any role for the B haplotype? [JOURNAL ARTICLE]
- J Clin Pathol 2014 Oct 28.
Contact of peripheral blood lymphocytes with Helicobacter pylori was proved to induce non- major histocompatibility complex-restricted cytotoxicity and natural killer cells are thought to play an important role in the immunity against H. pylori.In this research, we investigated any possible association between killer immunoglobulin-like receptors (KIR) genotypes and H. pylori infection.KIR genotype was analysed in 101 Lebanese symptomatic patients (51 H. pylori positive and 50 H. pylori-negative) using the KIR Genotyping SSP kit.Among the H. pylori-positive patients, the AA, AB and BB genotypical frequencies were, respectively, 43.14%, 41.18% and 15.68% with an A:B ratio of 1.76:1. The AA, AB and BB genotypes frequencies for H. pylori-negative individuals were 18%, 62% and 20%, respectively, with an A:B ratio of 0.96:1. No significant difference between patients and controls was detected.We noticed a reduced distribution of A haplotype among the 'H. pylori-negative' patients as compared with the "H. pylori-positive" group. This is the first study in the international literature that targets the correlation between KIR genotypes and H. pylori.