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Journal of clinical pathology [journal]
- Gene of the month: Interleukin 6 (IL-6). [JOURNAL ARTICLE]
- J Clin Pathol 2014 Jul 16.
The Interleukin 6 (IL-6) gene encodes the classic proinflammatory cytokine IL-6. It is also known as interferon-β2 (IFN-β2), B cell stimulatory factor-2 and hybridoma/plasmacytoma growth factor. IL-6 is a multifunctional cytokine with a central role in many physiological inflammatory and immunological processes. Due to its major role in initiation as well as resolving inflammation, deregulation of IL-6 is a mainstay of chronic inflammatory and autoimmune diseases. Additionally, IL-6 has been shown to be implicated in pathogenesis of many human malignancies. Thus, a better understanding of IL-6 and its role in various pathological conditions could enable the development of strategies to use it as a therapeutic target. This short review focuses on the structure, regulation and biological activities of IL-6. In addition we discuss the role of IL-6 in diseases with inflammatory background and cancer and also the therapeutic applications of anti-IL-6 agents.
- Message in a bottle: decoding medication injury patterns in the gastrointestinal tract. [REVIEW]
- J Clin Pathol 2014 Jul 15.
Medication injury in the gastrointestinal tract (GIT) is a rapidly evolving topic. Increasing endoscopy together with an ageing population, polypharmacy, and a burgeoning drug industry offer heightened opportunities to observe the unintended side effects of therapeutic ingestants. In this review, we emphasise the most commonly encountered medication injuries involving the GIT, as well as emerging agents and mimics. While topics are organised by organ system, the reader should keep in mind that injury patterns are generally not site-specific. As such, awareness of these major morphologic patterns can be translated to multiple tissue sites to more broadly facilitate the diagnostic process.
- Elevation of human ERV3-1 env protein expression in colorectal cancer. [LETTER]
- J Clin Pathol 2014 Jul 12.
- Gains of chromosomes 7 and 17 in tubulocystic carcinoma of kidney: two cases with fluorescence in situ hybridisation analysis. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Jul 11.
Tubulocystic carcinoma (TCC) is a very rare renal tumour with unique gross and microscopic features, alternatively considered as low-grade collecting duct carcinoma. Recent studies favoured distinction of TCC from collecting duct carcinoma, and some cases of TCC synchronously coexisting with other renal cell tumour subtypes were described. We report here two new cases of pure (case 1) or mixed (case 2) TCC with fluorescence in situ hybridisation (FISH) analysis, which showed gains of chromosomes 7 and 17 in the pure TCC of case 1, as well as in the TCC and the papillary renal cell carcinoma (PRCC) components in case 2. These data may further support the notion that TCC is more closely related to PRCC.
- Guidance for laboratories performing molecular pathology for cancer patients. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Jul 10.
Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here.
- Circulating tumour cells and the epithelial mesenchymal transition in colorectal cancer. [REVIEW]
- J Clin Pathol 2014 Jul 9.
Circulating tumour cells (CTCs) hold great potential as liquid biopsies to prognosticate disease and guide treatment in colorectal cancer. However, their emerging role in determining the molecular phenotype of tumour metastasis carries even more promising clinical use in the provision of comprehensive biomarker detection for targeted therapies and determination of drug resistance. The isolation of CTCs is technology dependent, and in the case of epithelial cell adhesion molecule-based platforms, the ability to detect cells that have undergone the epithelial to mesenchymal transition (EMT) is ineffective. CTCs displaying a mesenchymal phenotype are believed to have an increased metastatic potential. The rarity of CTCs provides another challenge in the enumeration of these cells. The future will likely involve the analysis of individual CTCs at any stage of the EMT in order to provide real-time phenotypic and molecular snapshots capable of tracking the dynamic evolution of tumour progression over time.
- Comparison of KRAS mutation analysis of colorectal cancer samples by standard testing and next-generation sequencing. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Jul 8.
Based on KRAS testing, the subset of patients with metastatic colorectal cancer (CRC) that could benefit from anti-EGFR therapy can be better delineated. Though KRAS testing has become significantly more prevalent over the last few years, methods for testing remain heterogeneous and discordance has been reported between methods.In this study, we examined a CRC patient population and compared KRAS testing done in Clinical Laboratory Improvement Amendments (CLIA) approved laboratories as part of standard clinical care and by next-generation sequencing (NGS) using the Illumina platform. Discordances were further evaluated with manual review of the NGS testing.Out of 468 CRC patient samples, 77 had KRAS testing done by both CLIA assay and NGS. There were concordant results between testing methodologies in 74 out of 77 patients, or 96% (95% CI 89% to 99%). There were three patient samples that showed discordant results between the two methods of testing. Upon further investigation of the NGS results for the three discordant cases, one sample showed a low level of the mutation seen in the standard testing, one sample showed low tumour fraction and a third did not show any evidence of the mutation that was found with the standard assay. Five patients had KRAS mutations not typically tested with standard testing.Overall there was a high concordance rate between NGS and standard testing for KRAS. However, NGS revealed mutations that are not tested for with standard KRAS assays that might have clinical impact with regards to the role for anti-EGFR therapy.
- Interobserver variability in assessing dysplasia and architecture in colorectal adenomas: a multicentre Canadian study. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Jul 8.
Following the introduction of colorectal cancer screening programmes throughout Canada, it became necessary to standardise the diagnosis of colorectal adenomas. Canadian guidelines for standardised reporting of adenomas were developed in 2011. The aims of the present study were (a) to assess interobserver variability in the classification of dysplasia and architecture in adenomas and (b) to determine if interobserver variability could be improved by the adoption of criteria specified in the national guidelines.An a priori power analysis was used to determine an adequate number of cases and participants. Twelve pathologists independently classified 40 whole-slide images of adenomas according to architecture and dysplasia grade. Following a wash-out period, participants were provided with the national guidelines and asked to reclassify the study set.At baseline, there was moderate interobserver agreement for architecture (K=0.4700; 95% CI 0.4427 to 0.4972) and dysplasia grade (K=0.5680; 95% CI 0.5299 to 0.6062). Following distribution of the guidelines, there was improved interobserver agreement in assessing architecture (K=0.5403; 95% CI 0.5133 to 0.5674)). For dysplasia grade, overall interobserver agreement remained moderate but decreased significantly (K=0.4833; 95% CI 0.4452 to 0.5215). Half of the cases contained high-grade dysplasia (HGD). Two pathologists diagnosed HGD in ≥75% of cases.The improvement in interobserver agreement in classifying adenoma architecture suggests that national guidelines can be useful in disseminating knowledge, however, the variability in the diagnosis of HGD, even following guideline review suggests the need for ongoing knowledge-transfer exercises.