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Journal-based learning exercises: CellularPathology/TransfusionScience


Journal-based learning (JBL) exercises are a regular feature of CPD coverage in The Biomedical Scientist. You may complete as many JBL exercises as you wish and are not restricted by specialty. Each article’s contents should be read, researched and understood and you should then come to a decision on each question. The pass mark is 17 out of 20 questions answered correctly. Journal-based learning exercises may be completed at any time until the published deadline date. Please select your choice of correct answers and complete the exercises online (www.ibms.org/go/practice-development/cpd/jbl).


DEADLINE: WEDNESDAY 2 NOVEMBER 2016


PD-L1 testing in lung cancer in the UK: recognizing the challenges for implementation. Cree IA, Booton R, Cane P et al. Histopathology 2016 May 19 (Epub ahead of print).


A Worldwide, almost 5.6 million people die from lung cancer every year. Non-small-cell lung cancer (NSCLC) accounts for around 5% of all cases but, until recently, options for managing this disease were limited and often ineffective.


B The advent of tyrosine-kinase inhibitors (TKIs) led to significant progress in NSCLC management.


C PD is programmed death receptor 1 and PD-L1 is its ligand.


D Several drugs have been approved or are in the late stages of development targeting PD-1 or PD-L1.


E Immune checkpoint inhibitors rely on specific targeting of the tumours.


F In the context of NSCLC, the binding of PD-1 and PD-L1 does not protect the tumour from immune attack.


G PD-1 is an example of an inhibitory receptor, which, when deactivated by its ligand (usually PD-L1 on cancer cells) blocks intracellular signalling.


H Quiescent T cells require stimulation by MHC proteins on antigen-presenting cells (APCs).


I Anti-PD-1 agents are pembrolizumab and nivolumab.


J Ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a suitable method for lung biopsy sampling.


K There is increasing evidence of homogeneity between primary tumours and metastases.


L In cases where NSCLC is suspected and there is no morphological evidence of squamous or glandular differentiation, a limited IHC panel (eg p40 and thyroid transcription factor-1) is recommended.


M Companion PD-L1 IHC assays/kits are available or in development, corresponding to the same checkpoint inhibitors for the treatment of PD-L1-positive NSCLC.


N The Dako assay kit (Dako 22C3 pharmDx) targeted at PD-1 links to nivolumab as the checkpoint inhibitor.


O In the UK, inter-observer variability in PD-L1 staining interpretation should be strictly monitored, with the recommendation that potential interpreters should review a sufficient number of cases to achieve a minimum concordance of 90%.


P For the PD-1 and PD-L1 assay, aspects of uncertainty should include sampling issues and the operator’s skill and judgement.


Q The use of controls with staining results close to the decision-making cut-off points is recommended.


R Any laboratory carrying out clinical PD-L1 IHC testing does not need to take part in an EQA as outlined by ISO 15189, as long as the laboratory is satisfied that the controls have worked.


S Expected PD-L1 positivity in the UK is currently 82.4%


T For one of the drugs in development, the biomarker test is based on the area of tumour infiltrated by PD-L1-positive immune cells, including tumour-infiltrating (non- neoplastic) cells.


THE BIOMEDICAL SCIENTIST AUGUST 2016 Assessment No 080716 TRUE FALSE


Expression levels of ABCG2 on cord red blood cells and study of fetal anemia associated with anti-Jr(a). Fujita S, Kashiwagi H, Tomimatsu T et al. Transfusion 2016; 56 (5): 1171–81.


A The Jr(a–) phenotype is more common among the Japanese population than other populations throughout the world.


TRUE FALSE


TRUE FALSE TRUE FALSE TRUE FALSE TRUE FALSE TRUE FALSE


B Only one mutation in the ABCG2 gene has been identified to cause the Jr(a–) phenotype.


C Anti-Jra has caused hydrops fetalis.


D The majority of fetal anaemia due to anti-Jra progressive in the later gestational ages.


and monoclonal anti-Jra erythroid colony formation.


F ABCG2 expression levels in cord RBCs are lower than those of adults.


G Using two examples of anti-Jra TRUE FALSE


TRUE FALSE TRUE FALSE


that had caused severe


haemolytic disease of the fetus and newborn (HDFN), there was an acceleration of RBC phagocytosis compared with anti-D.


H The Jra antigen is most likely to be expressed on the third extracellular loop of the ABCG2 molecule.


I The expression levels of ABCG2 in cord RBCs tend to decrease in the later gestational ages.


TRUE FALSE TRUE FALSE


J Haemolysis is the main cause of anaemia due to anti-Jra K Binding of anti-Jra to RBCs expressing high amounts of ABCG2 may cause apoptosis. TRUE FALSE


L ABCG2 transports multiple molecules, including hemin, which contains iron, and iron transportation is essential for erythropoiesis.


M ABCG2 is indispensable for erythropoiesis, as both Jr(a–) subjects and ABCG2 knockout mice develop anaemia.


TRUE FALSE TRUE FALSE


N The decrease of ABCG2 expression during gestation appears to be largely due to the change in cell size.


O It has been reported that mRNA and protein levels of ABCG2 in the human placenta increase towards the end of gestation.


P Mild fetal anaemia due to anti-Jra TRUE FALSE Q Anti-Jra


TRUE FALSE TRUE FALSE


is likely to be overlooked


by obstetricians because it may resolve spontaneously. has seldom caused significant haemolytic


transfusion reactions after transfusion of Jr(a+) red cells.


R Feline RBCs express a higher amount of ABCG2 than do human RBCs.


S The density of ABCG2 protein in cord RBCs changes dramatically during gestation.


T Epitopes of anti-Jra of fetal anaemia.


TRUE FALSE TRUE FALSE


REFLECTIVE LEARNING QUESTIONS – See opposite 441 correlate well with the incidence .


TRUE FALSE TRUE FALSE TRUE FALSE TRUE FALSE TRUE FALSE


TRUE FALSE TRUE FALSE


may not be


E Using a colony-forming assay, both maternal sera containing anti-Jra


suppressed TRUE FALSE Assessment No 080216


TRUE FALSE TRUE FALSE TRUE FALSE TRUE FALSE


TRUE FALSE TRUE FALSE TRUE FALSE


TRUE FALSE TRUE FALSE TRUE FALSE TRUE FALSE TRUE FALSE


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