Anatomical Pathology
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Browsing Anatomical Pathology by Subject "Breast -- Cancer -- Diagnosis"
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- ItemAnalysis of the clinical utility of gene expression profiling in relation to conventional prognostic markers in South African patients with breast carcinoma(Stellenbosch : Stellenbosch University, 2014-12) Grant, Kathleen Ann; Kotze, Maritha J.; Wright, Colleen A.; Apffelstaedt, Justus P.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Anatomical Pathology.ENGLISH ABSTRACT: Breast cancer is a heterogeneous disease characterised by marked inter-individual variability in presentation, prognosis and clinical outcome. The recognition that morphological assessment has limited utility in stratifying patients into prognostic subgroups led to clinico-pathological classification of tumour biology, based on receptor expression using immunohistochemical (IHC) techniques. This standard is currently complemented by the development of gene expression profiling methodology that led to the identification of intrinsic molecular subtypes, reflecting tumour genetics as the true driver of biological activity in breast cancer. The study was based on the hypothesis that molecular classification of breast carcinomas integrated with established clinico-pathological risk factors will improve current diagnostic and risk management algorithms used in clinical decision-making. A pathology-supported genetic testing strategy was used to evaluate microarray-based gene profiling against diagnostic pathology techniques as the current standard. Clinico-pathological factors including age, number of positive axillary nodes, tumour size, grade, proliferation index and hormone receptor status was documented for 141 breast cancer patients (143 tumours) referred for microarray-based gene expression profiling between 2007 and 2014. Subsets of patients were selected from the database based on the inclusion criteria defined for three phases in which the study was performed, in order to determine 1) the percentage of patients stratified as having a low as opposed to high risk of distant recurrence using the 70-gene MammaPrint profile within the inclusion criteria, 2) correlation of HER2 status as determined by IHC and fluorescence in situ hybridisation (FISH) with microarray-based mRNA readout (TargetPrint), and 3) the relationship between hormone receptor determination as reported by standard IHC and molecular subtyping using the 80-gene BluePrint profile. Similar distribution patterns for MammaPrint low- and high-risk profiles were obtained irrespective of whether fresh tumour biopsies or formalin-fixed paraffin embedded (FFPE) tissue was used. During the first phase of the study, 60% of the 106 tumour specimens analysed with MammaPrint were classified as low-risk and 40% as high-risk using a newly-developed MammaPrint pre-screen algorithm (MPA) aimed at cost-saving. In the second phase of the study, performed in 102 breast tumours, discordant or equivocal HER2 results were found in four cases. Reflex testing confirmed the TargetPrint results in discordant cases, achieving 100% concordance regardless of whether fresh tumour or FFPE tissue was used for microarray analysis. For the third phase of the study 74 HER2-negative tumour samples were selected for comparative analysis. Statistically significant positive correlations were found between protein expression (IHC score) and mRNA (TargetPrint) levels for estrogen receptor (ER) (R=0.53, p<0.0001) as well as progesterone receptor (PR) (R=0.62, p<0.0001), while combined ER/PR tumour status was reported concordantly in 82.4% of these tumours. BluePrint was essential for interpretation of these results used in treatment decision-making. The MPA developed in South Africa in 2009 was validated in this study as an appropriate strategy to prevent chemotherapy overtreatment in patients with early-stage breast cancer. The use of microarray-based analysis proved to be a reliable ancillary method of assessing HER2 status in breast cancer patients. Risk reclassification based on the TargetPrint results helped to avoid unnecessary high treatment costs in false-positive cases, in addition to providing potentially life-saving treatment to those for whom it was indicated. While neither IHC nor TargetPrint estimation of intrinsic subtype correlated independently with the molecular subtype as indicated by BluePrint profiling, the ability to distinguish between basal-like and luminal tumours was enhanced when the combined protein and mRNA values was considered. Genomic profiling provided information over and above that obtained from routine clinico-pathological assessments. This finding supports the relevance of a pathology-supported genetic testing approach to breast cancer management, whereby advanced genomic testing is combined with existing clinico-pathological risk stratification methods for improved patient management.
- ItemChemotherapy naive breast cancer: a correlation study between BD Cytorich™ Red cell blocks and formalin- fixed paraffinembedded tissue blocks(Stellenbosch : Stellenbosch University, 2019-04) Van Rooyen, Evelyn; Schubert, Pawel T.; Schneider, Johann; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Anatomical Pathology.Background: The ever increasing burden of breast cancer, the most common cancer among women, demands a diagnostic test that is rapid, reliable, informative and cost-effective; particularly in countries with limited financial and medical resources. FNAB cytology and cell block combination has gained worldwide utility and has been described to be accurate and reliable. Aim: Henceforth the aim of this study was to retrospectively correlate the expression of prognostication markers, namely, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) performed on cell blocks (using the BD CytorichTM Red method) and formalin-fixed, paraffin-embedded cell blocks (FFPET) in chemotherapy naive breast carcinomas, by immunochemistry (immunocytochemistry and immunohistochemistry respectively) and to perform fluorescence in-situ hybridization (FISH) testing for over- expression of the HER2 gene. Methods: Between 2013 and 2016, 132 cases of primary breast carcinoma were identified that had both cytology (including Cytorich™ Red cell blocks) and histology specimens that were both chemotherapy naive. Immunostaining for ER, PR and HER2 was performed. The staining was scored according to the Allred scoring system for histology specimen and this system was slightly adapted for cytology specimens, which also took the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines into account. FISH for HER2 over-expression was performed. The grade of the carcinoma was also analysed on both the cytology specimens (using the Robertson’s grading system) and the histology specimens (using the Modified Elston & Ellis system). Results: ER and PR performed on cell blocks had good correlation with FFPET with 91% and 85% sensitivity, respectively. HER2 on cell blocks had an agreement of 88% with FFPET. 87.88% of cell blocks had more than a 100 tumour cells present on H&E sections and cytological grading had an agreement of 41.41% with histological grading. Conclusion: The cell block technique continues to play a vital role in the diagnosis of primary, recurrent and metastatic breast carcinoma, allowing assessment of prognosis and prediction of response to therapy.
- ItemAn evaluation of the diagnostic adequacy and immunocytochemistry of manual liquid-based smears in breast aspirates(Medpharm Publications, 2013) Shibemba, A. L.; Wright, C. A.; Bezuidenhout, J.; Schubert, P. T.The aim of this study was to determine if the Syner-Med®/Cell-Solutions® liquid-based cytology (LBC) technique would provide adequate diagnostic material when applied to breast fine-needle aspiration biopsy (FNAB) specimens and to determine its suitability for immunocytochemistry. A prospective study was undertaken of 38 consecutive patients who underwent FNAB of breast masses in the Fine Needle Aspiration Clinic at Tygerberg Hospital, Cape Town, over a period of six months. Conventional smear cytology slides (CSC) were formulated and the material that remained in the needle was used to prepare the LBC Syner-Med®/Cell-Solutions® slides. The CSC and LBC slides were evaluated by two pathologists. The assessed parameters were cellularity, background and representative diagnostic material. Immunocytochemical stains for pancytokeratin (MNF-116) and oestrogen receptor were performed in each case. In 33 cases (87%), LBC compared favourably with CSC. Adequacy rates of 84.2% for CSC and 76.3% for LBC were found. A diagnosis was made in 78.9% of the CSC cases and in 71% of the LBC cases. The LBC slides showed excellent results, with immunocytochemical staining for MNF-116 and oestrogen receptor. The Syner-Med®/Cell-Solutions® LBC fixative and preparation method provides an alternative technique for obtaining well fixed and prepared slides that are suitable for diagnostic cytology and immunocytochemistry.
- ItemExome sequencing in a family with luminal-type breast cancer underpinned by variation in the methylation pathway(MDPI, 2017-02-22) Van der Merwe, Nicole; Peeters, Armand V.; Pienaar, Fredrieka M.; Bezuidenhout, Juanita; Van Rensburg, Susan J.; Kotze, Maritha J.ENGLISH ABSTRACT: Panel-based next generation sequencing (NGS) is currently preferred over whole exome sequencing (WES) for diagnosis of familial breast cancer, due to interpretation challenges caused by variants of uncertain clinical significance (VUS). There is also no consensus on the selection criteria for WES. In this study, a pathology-supported genetic testing (PSGT) approach was used to select two BRCA1/2 mutation-negative breast cancer patients from the same family for WES. Homozygosity for the MTHFR 677 C>T mutation detected during this PSGT pre-screen step was considered insufficient to cause bilateral breast cancer in the index case and her daughter diagnosed with early-onset breast cancer (<30 years). Extended genetic testing using WES identified the RAD50 R385C missense mutation in both cases. This rare variant with a minor allele frequency (MAF) of <0.001 was classified as a VUS after exclusion in an affected cousin and extended genotyping in 164 unrelated breast cancer patients and 160 controls. Detection of functional polymorphisms (MAF > 5%) in the folate pathway in all three affected family members is consistent with inheritance of the luminal-type breast cancer in the family. PSGT assisted with the decision to pursue extended genetic testing and facilitated clinical interpretation of WES aimed at reduction of recurrence risk.