ABSTRACT
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) over-expression in breast cancer is associated with aggressive tumor behavior and predicts response to targeted therapy. Accurate HER2 result is paramount for optimal patient management. However, routine HER2 immunohistochemistry (IHC) testing are subjected to intra- and inter-laboratory variability. 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.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Carcinoma/genetics , Carcinoma/metabolism , Genes, erbB-2 , Immunohistochemistry/statistics & numerical data , Receptor, ErbB-2/metabolism , Adult , Aged , Aged, 80 and over , Female , Genetic Variation , Humans , Immunohistochemistry/methods , Middle Aged , Reproducibility of ResultsSubject(s)
Liver Failure, Acute/etiology , Metabolism, Inborn Errors/genetics , Transaldolase/deficiency , Transaldolase/genetics , Genes , Heterozygote , Humans , Infant, Newborn , Liver Failure, Acute/diagnosis , Liver Failure, Acute/metabolism , Male , Metabolism, Inborn Errors/complications , Metabolism, Inborn Errors/diagnosis , Monosaccharides/urine , Mutation, Missense , Pentose Phosphate Pathway/genetics , Polymers/metabolism , Transaldolase/metabolismABSTRACT
BACKGROUND: Promising new pharmacological agents and gene therapy targeting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) could modulate treatment of colorectal cancer in the future. The aim of this study was to elucidate the expression fo beta-catenin and teh presence of COX-2 and iNOS in colorectal cancer specimens in Malaysia. This is a useful prelude to future studies investigating interventions directed towards COX-2 adn iNOS. METHODS: A cross-section study using retrospective data over a 2-year period (1999-2000) involved 101 archival, formalin-fixed, paraffin-embedded tissue samples of colorectal cancers that were surgically resected in a tertiary referral. RESULTS: COX-2 production was detected in adjacent normal tissue in 34 sample (33.7%) and in tumour tissue in 60 samples (59.4%). More tumours expressed iNOS (82/101, 81.2%) than COX-2. No iNOS expression was detected in adjacent normal tissue. Intense beta-catenin immunoreactivity at the cell-to-cell border. Poorly differentiated tumours had significantly lower total beta-catenin (p = 0.009) and COX-2 scores (p = 0.031). No significant relationships were established between pathological stage and beta-catenin, COX-2 and iNOS scores. CONCLUSIONS: the accumulation of beta-catenin does not seem to be sufficient to activate pathways that lead to increased COX-2 and iNOS expression. A high proportion of colorectal cancers were found to express COX-2 and a significant number produced iNOS, suggesting that their inhibitors may be potentially useful as chemotherapeutic agents in the management of colorectal cancer.
Subject(s)
Colorectal Neoplasms/metabolism , Cytoskeletal Proteins/metabolism , Isoenzymes/metabolism , Nitric Oxide Synthase/metabolism , Prostaglandin-Endoperoxide Synthases/metabolism , Trans-Activators/metabolism , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/pathology , Cross-Sectional Studies , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/therapeutic use , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Isoenzymes/antagonists & inhibitors , Malaysia , Male , Membrane Proteins , Middle Aged , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase Type II , Retrospective Studies , Statistics, Nonparametric , beta CateninABSTRACT
OBJECTIVES: This study was carried out to determine the role of p53 and p21 in the pathogenesis of prostatic adenocarcinoma and their association with tumour grade. METHOD: Sixty-seven histologically confirmed prostatic adenocarcinoma cases collected from Hospital Universiti Kebangsaan Malaysia and General Hospital Kuala Lumpur were studied. The formalin-fixed paraffin-embedded tissues were stained with monoclonal antibody p53 (clone DO-7) and p21 (clone SX II8) using standard avidin-biotin complex immunohistochemistry (IHC) after microwave antigen retrieval. The adenocarcinomas were graded histologically according to Gleason score: low grade = score 2-4, intermediate grade = score 5-7, high grade = score 8-10. Histological grade was analysed against IHC expressions of p53 and p21 and against patient age and ethnicity. RESULTS: IHC positivity for p53 was expressed in 1/2 (50%) low grade, 14/33 (42%) intermediate grade, and 21/32 (66%) high grade tumours. p21 was expressed in 0/2 low grade, 16/33 (48%) intermediate grade and 15/32 (47%) high grade tumours. p53 and p21 expressions did not show statistically significant correlation with the different grades of prostatic adenocarcinoma or with each other (p = 0.42). There was no correlation between tumour grade and age or ethnicity. CONCLUSION: Although the p53 positivity rate was higher in high-grade prostate adenocarcinoma, this was not statistically significant. We found that a combined expression of p21 and p53 was not correlated with tumour grade. We could not confirm that p21 expression was dependent on p53 expression.