Objective: This study aims to determine inter-laboratory variation in HER2 IHC testing through a slide-exchange program between five main reference laboratories.
Method: A total of 20 breast carcinoma cases with different known HER2 expression and gene status were selected by the central laboratory in five testing rounds. Three unstained tissue sections from each case were sent to participating laboratories, which immunostained and interpreted the HER2 immunohistochemistry result. One of the stained slides was sent to one designated participating laboratory for evaluation. Results were analyzed by the central laboratory.
Results: A complete concordance was achieved in six IHC-positive and six IHC-negative cases, its gene status of which was confirmed by in-situ-hybridization (ISH) study. The discordant results were observed in six equivocal cases, one negative case and one positive case with a concordance rate of 50-88.3%. Interestingly, the negative discordant case actually displays tumor heterogeneity. Good inter-observer agreement was achieved for all participating laboratories (k = 0.713-1.0).
Conclusion: Standardization of HER2 testing method is important to achieve optimum inter-laboratory concordance. Discordant results were seen mainly in equivocal cases. Intra-tumoral heterogeneity may impact the final HER2 IHC scoring. The continuous quality evaluation is therefore paramount to achieve reliable HER2 results.
Case Description: We report a 42-year-old man, diagnosed with rosette-forming glioneuronal tumor of the fourth ventricle with a positive isocitrate dehydrogenase 1 mutation, progressed to glioblastoma after 6 years from diagnosis. We discuss the clinical history, radiological findings, and histopathological characteristic with immunohistochemistry findings observed in this unique case.
Conclusions: Despite being acceptable as benign, based on our observations in this case, there is a potential for malignant transformation of rosette-forming glioneuronal tumor. The role of isocitrate dehydrogenase 1 mutation leading to malignant transformation could not be established as our finding is novel and further prospective studies are required to prove this association.
Methods: A total of 100 formalin-fixed paraffin-embedded urothelial carcinoma tissues were selected from the Department of Pathology, Hospital Kuala Lumpur and the protein expression of ISL1 and LHX5 was determined using immunohistochemistry.
Results: Positive expression of ISL1 and LHX5 was detected in 94% and 98% of the samples, respectively. There were no distinct LHX5 expression patterns associated with different cancer stages, but the proportion of high-expressing tumours was higher in high-grade tumours. In addition, there was a significant association between the expression of LHX5 and tumour grade. The proportion of tumours expressing high levels of ISL1 was found to be highest in later stage tumours.
Conclusion: The high percentage of tumours expressing both these genes suggests that ISL1 and LHX5 play an important role in bladder tumourigenesis across multiple stages.