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Journal of clinical pathology [journal]
- Clinical utility of selective molecular genotyping for diagnosis of partial hydatidiform mole; a retrospective study from a regional trophoblastic disease unit. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Jul 30.
Hydatidiform moles (HMs) are genetically abnormal conceptions, associated with increased risk of gestational trophoblastic neoplasia. Diagnosis is usually based on histopathological criteria but in a minority definitive histological diagnosis is not possible; in such cases molecular genotyping may be diagnostic. This study describes the clinical usefulness of such an approach.Cases in which central histology review demonstrated abnormal villous morphological features insufficient for definite diagnosis of partial HM (PHM) ('favour PHM' or 'PHM not excluded') underwent molecular genotyping of villous and maternal tissue, using short tandem repeats, to determine ploidy and parental origin of the placental tissue.Of 251 cases with non-diagnostic morphological villous abnormalities, molecular investigation was not possible in 14 (6%; limited material or technical issues). Overall, 124 (49%) were triploid including 71/86 (85%) of those morphologically favouring PHM, and 53/165 (32%) of those favouring non-molar miscarriage. Of 85 cases of triploidy in whom sufficient material was available, 84 had an additional paternal contribution. Single cases of digynic triploidy, tetraploid PHM and two mosaic conceptions were also identified. Twenty-three non-molar diploid cases (21%) exhibited trisomy.Molecular genotyping allows definitive diagnosis of PHM for cases in which specialist histopathology review remains equivocal. While this approach provides definite diagnosis it is considerably more expensive than a pragmatic management approach of human chorionic gonadotrophin surveillance in all such cases.
- Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Jul 30.
Adrenocortical carcinoma (ACC) carries a poor prognosis and current systemic cytotoxic therapies result in only modest improvement in overall survival. In this retrospective study, we performed a comprehensive genomic profiling of 29 consecutive ACC samples to identify potential targets of therapy not currently searched for in routine clinical practice.DNA from 29 ACC was sequenced to high, uniform coverage (Illumina HiSeq) and analysed for genomic alterations (GAs).At least one GA was found in 22 (76%) ACC (mean 2.6 alterations per ACC). The most frequent GAs were in TP53 (34%), NF1 (14%), CDKN2A (14%), MEN1 (14%), CTNNB1 (10%) and ATM (10%). APC, CCND2, CDK4, DAXX, DNMT3A, KDM5C, LRP1B, MSH2 and RB1 were each altered in two cases (7%) and EGFR, ERBB4, KRAS, MDM2, NRAS, PDGFRB, PIK3CA, PTEN and PTCH1 were each altered in a single case (3%). In 17 (59%) of ACC, at least one GA was associated with an available therapeutic or a mechanism-based clinical trial.Next-generation sequencing can discover targets of therapy for relapsed and metastatic ACC and shows promise to improve outcomes for this aggressive form of cancer.
- An evaluation of Neisseria gonorrhoeae antimicrobial susceptibility testing in the UK. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Jul 30.
The only method currently available to perform Neisseria gonorrhoeae antimicrobial susceptibility testing (Ng-AST) requires a viable organism obtained by culture. Reports of in vitro resistance to extended-spectrum cephalosporins, the treatment of choice for gonorrhoea, coupled with increasing gonorrhoea diagnoses is worrying. The aim of this study was to identify various methodologies employed by the UK microbiology laboratories to perform Ng-AST. Of the 118 laboratories that responded, 114 offered Ng-AST; the majority (82.5%, 94/114) of the laboratories used British Society for Antimicrobial Chemotherapy methodology for Ng-AST. The other main findings were infrequent use of quality control procedures and inconsistent susceptibility testing of the antibiotics used routinely for treatment.
- The significance of autophagy in colorectal cancer pathogenesis and implications for therapy. [REVIEW]
- J Clin Pathol 2014 Jul 23.
Colorectal cancer (CRC) is one of the most common cancers in developed countries with poor survival outcome in advanced stages of the disease due to its resistance to chemotherapy and other forms of treatment. New and alternative approaches are needed to overcome the tumour cells' capacity for survival and to drive the tumour towards cell death. Autophagy is a mechanism involved in the elimination of damaged cellular components through lysosomal degradation and is capable of inducing programmed cell death. The process has recently gained much interest in understanding the pathogenesis of CRC and its potential for treatment of the disease due to its role in host protection and anticancer activity. This review describes and illustrates the fundamental mechanisms of autophagy, its importance as a prognostic marker and the current approaches to harness its protective and anticancer activity in CRC therapy.
- Gastric neuroendocrine neoplasms and related precursor lesions. [REVIEW]
- J Clin Pathol 2014 Jul 22.
Gastric neuroendocrine neoplasms (NENs) are a heterogeneous group of tumours showing different clinicopathological features and behaviour, implying a wide spectrum of therapeutic options. They are currently classified using the 2010 WHO classification of digestive neuroendocrine neoplasms into G1-neuroendocrine tumours (NETs), G2-NETs, neuroendocrine carcinomas (NECs) and mixed adenoneuroendocrine carcinomas (MANECs). However, most gastric NENs are composed of ECL-cells (ECL-cell NETs) that can be preceded by ECL-cell hyperplastic and dysplastic lesions, whose oncologic potential has not yet been completely elucidated. ECL-cell NETs differ considerably in terms of prognosis depending on the proliferative status and clinicopathological background. The integration of both aspects in the diagnostic pathway may help to better classify tumours in different prognostic categories, especially when diagnosing them in small bioptic specimens. NECs are all poorly differentiated, highly aggressive carcinomas, while MANECs can show different morphological features that are directly associated with different prognoses. Precursor lesions of such carcinomas are not entirely understood. In this review, the clinicopathological features of gastric NENs and related precursor lesions will be described to give the reader a comprehensive overview on this topic.
- p-mTOR expression is associated with better prognosis in luminal breast carcinoma. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Jul 22.
Despite considerable interest in the PI3K/AKT/mTOR pathway in breast carcinomas (BC), published data reports contradictory results regarding the association of phosphorylated mammalian target of Rapamycin (p-mTOR) expression with clinico-pathological features and prognosis in BC. Here, we evaluate the main clinico-pathological associations with p-mTOR expression in BC, with focus on the different molecular subtypes.In this retrospective study, 331 BC patients were included in final analysis. Outcome measures included disease-free survival (DFS) and overall survival (OS) times. Baseline data and outcome measures were compared between immunohistochemical p-mTOR expressing and non-expressing BCs. Subgroup analysis was performed to assess the effect of p-mTOR expression in the outcome for each BC molecular subtype.43.8% of the tumours were positive for p-mTOR, with a significant correlation between p-mTOR expression with smaller (<2 cm) (p=0.021) and lower-grade tumours (p<0.001). Expression of p-mTOR was also associated with longer DFS (HR of 0.32, p<0.001) and OS (HR of 0.20, p<0.001). In a multivariable analysis, the HR remained significant with minimal change (HR=0.26, p=0.002 for OS; HR=0.40, p=0.002 for DFS). In subgroup analysis, luminal p-mTOR-expressing tumours demonstrated longer DFS and OS (HR 0.33, p=0.003; HR 0.20, p=0.003, respectively) independently of size, grade, lymph node status and Her-2 overexpression.p-mTOR expression is associated with smaller, lower-grade and with luminal BC. In multivariable analysis, p-mTOR expression was associated with longer DFS and OS, independently of the size, grade and lymph node status, especially in luminal BCs.
- Second opinion in breast pathology: policy, practice and perception. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Jul 22.
To assess the laboratory policies, pathologists' clinical practice and perceptions about the value of second opinions for breast pathology cases among pathologists practising in the USA.Cross-sectional data were collected from 252 pathologists who interpret breast specimens in eight states using a web-based survey. Descriptive statistics were used to characterise findings.Most participants had >10 years of experience interpreting breast specimens (64%), were not affiliated with academic centres (73%) and were not considered experts by their peers (79%). Laboratory policies mandating second opinions varied by diagnosis: invasive cancer 65%; ductal carcinoma in situ (DCIS) 56%; atypical ductal hyperplasia 36% and other benign cases 33%. 81% obtained second opinions in the absence of policies. Participants believed they improve diagnostic accuracy (96%) and protect from malpractice suits (83%), and were easy to obtain, did not take too much time and did not make them look less adequate. The most common (60%) approach to resolving differences between the first and second opinion is to ask for a third opinion, followed by reaching a consensus.Laboratory-based second opinion policies vary for breast pathology but are most common for invasive cancer and DCIS cases. Pathologists have favourable attitudes towards second opinions, adhere to policies and obtain them even when policies are absent. Those without a formal policy may benefit from supportive clinical practices and systems that help obtain second opinions.
- Caution over use of ES2 as a model of ovarian clear cell carcinoma. [LETTER]
- J Clin Pathol 2014 Jul 21.
- 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.