ABSTRACT
CONTEXT: The incidence of colorectal cancers (CRCs) in young Indian patients is higher than the international average. CRCs in young patients are commonly of mucinous type and show microsatellite instability (MSI). AIMS: To ascertain the MSI status of mucinous CRCs in patients ≤40 years of age by molecular testing and to correlate this with immunohistochemical (IHC) analysis and tumor histology. SUBJECTS AND METHODS: Archived formalin-fixed paraffin embedded tissue blocks of 30 young mucinous CRC patients were retrieved. MSI testing was done using two mononucleotide markers – BAT26 and NR24. IHC analysis was done using MLH1, MSH2, and MSH6. Histological features of all cases were studied. Data were analyzed using the SPSS software and the Pearson's chi-square test and Fisher's exact test. RESULTS: Eight out of 30 cases (26.7%) showed MSI by molecular testing. IHC identified seven of these cases. Histological features showing a statistically significant association with MSI were the presence of a well-differentiated adenocarcinoma component (P = 0.003), peritumoral lymphocytes (P = 0.002) and tumor budding (P = 0.021). CONCLUSION: The detection of defective mismatch repair (MMR) proteins using IHC for MLH1, MSH2, and MSH6 and molecular testing using BAT26 and NR24 appears to be a good protocol to detect CRCs with MSI. Histology could be useful in identifying cases that require screening for presence of MMR protein defects
ABSTRACT
Introduction: Acquired bleeding disorders are a major causeof mortality, both in the developed and developing countries.An acute haemorrhage should be managed immediately withblood products, factor concentrates or anti-fibrinolytics.Investigations to detect coagulopathies typically includebaseline screening tests like prothrombin time, activatedpartial thromboplastin time, platelet count and fibrinogenlevel. These tests have a long turn around time whichfrequently lead to a blinded approach towards blood productsupport leading to under or over transfusion. In contrast,rotational thromboelastometry (ROTEM) which assesseshaemostasis from the start of clot formation to fibrinolysisgives earliest results within ten minutes. This study wasdone to establish a correlation between ROTEM parametersand standard coagulation profile in the context of acquiredbleeding disorders.Material and Methods: A total of 138 subjects - 70 patientswho presented with acquired bleeding disorders and 68 subjectsdiagnosed to be normal on the basis of a complete coagulationwork up were included as the cases and controls respectively.All samples were subjected to standard coagulation profileand ROTEM analysis which included Clotting Time, ClotFormation Time, Alpha Angle, Maximum Clot Firmness andMaximum Lysis.Results: The Maximum Clot Firmness had a very goodco relation with serum fibrinogen levels (k value - 0.807;p<0.000; Sensitivity - 88%; Specificity - 92%), and goodcorrelation with platelet count (k value - 0.793; p< 0.000;Sensitivity - 86%, Specificity-92%), whereas Clot FormationTime showed moderate correlation with aPTT. Clotting timehad a poor correlation with prothrombin time and activatedpartial thromboplastin time.Conclusion: The achievement of haemostasis is a crucialfactor for determining patient outcomes in acquired bleedingdisorders. The gold standard test to diagnose coagulopathy is thestandard coagulation profile. Rotational thromboelastometrycorrelates well with standard coagulation parameters. Thistest which is performed on whole blood showed interpretableresults within 10 minutes, whereas standard coagulationprofile required an average of 45 – 75 minutes. In view of thegood correlation to the standard coagulation profile, it appearsthat Rotational Thromboelastometry results can be safely usedto implement early transfusion therapy for haemorrhage.