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- Gremel, Gabriela, et al.
(författare)
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A systematic analysis of commonly used antibodies in cancer diagnostics
- 2014
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 64:2, s. 293-305
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Tidskriftsartikel (refereegranskat)abstract
- AimsImmunohistochemistry plays a pivotal role in cancer differential diagnostics. To identify the primary tumour from a metastasis specimen remains a significant challenge, despite the availability of an increasing number of antibodies. The aim of the present study was to provide evidence-based data on the diagnostic power of antibodies used frequently for clinical differential diagnostics. Methods and resultsA tissue microarray cohort comprising 940 tumour samples, of which 502 were metastatic lesions, representing tumours from 18 different organs and four non-localized cancer types, was analysed using immunohistochemistry with 27 well-established antibodies used in clinical differential diagnostics. Few antibodies, e.g. prostate-specific antigen and thyroglobulin, showed a cancer type-related sensitivity and specificity of more than 95%. A majority of the antibodies showed a low degree of sensitivity and specificity for defined cancer types. Combinations of antibodies provided limited added value for differential diagnostics of cancer types. ConclusionsThe results from analysing 27 diagnostic antibodies on consecutive sections of 940 defined tumours provide a unique repository of data that can empower a more optimal use of clinical immunohistochemistry. Our results highlight the benefit of immunohistochemistry and the unmet need for novel markers to improve differential diagnostics of cancer.
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| 2. |
- Pekar, Gyula, et al.
(författare)
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Biobanking multifocal breast carcinomas : sample adequacy with regard to histology and DNA content
- 2016
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 68:3, s. 411-421
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To determine the volume of tumoral and normal breast tissue containing sufficient DNA (>2 μg/sample) for genetic platforms and biobanking, with a focus on multifocality, tumoral heterogeneity, and factors that critically influence sample acceptability.METHODS AND RESULTS: We examined 57 breast surgical specimens with multifocal (46/57) and unifocal (11/57) cancers. Punch biopsies were obtained from tissue slices under multimodal radiological guidance, and the colour-coded sampling sites were identified in large-format histology slides. The study comprised 415 DNA isolations from tumour (n = 105) and normal (n = 283) tissue, including skin (n = 27) samples. A single 2-mm core from invasive tumour contained sufficient DNA in 91.4% (96/105) of cases, depending on tumour type (3.8-108.2 μg/sample), number and size of additional foci in multifocal cases (P = 0.001), tumour consistency, and degree of necrosis. Three biopsies obtained with a 4-mm device were required from normal breast tissue, at least 10 mm from the tumour. Cold ischaemia for up to 82 min did not influence the yield of DNA.CONCLUSIONS: Radiological disease mapping is useful for guiding optimal specimen slicing and for targeting breast lesions. A single 2-mm core from tumour and multiple 4-mm cores from normal breast tissue yield adequate DNA in the majority of samples.
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| 3. |
- Pekar, Gyula, et al.
(författare)
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Equivocal (HER2 IHC 2+) breast carcinomas : gene-protein assay testing reveals association between genetic heterogeneity, individual cell amplification status and potential treatment benefits
- 2019
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Ingår i: Histopathology. - : WILEY. - 0309-0167 .- 1365-2559. ; 74:2, s. 300-310
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Genetic heterogeneity can pose a challenge to identifying eligible cases for targeted therapy in the human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 2+ breast carcinoma group. In this study, we characterised this subset of tumours according to clinicopathological parameters.Methods and results: We assessed 1000 tumour cells per case and recorded the number of HER2 and chromosome enumeration probe 17 (CEP17) copies using gene-protein assay slides. HER2 status was determined based on ASCO/CAP 2013 guidelines. Tumours with 5-50% of cancer cells with amplification were considered to be heterogeneous, whereas those with >50% were considered to be non-heterogeneous. In a study cohort of 110 HER2 IHC 2+ carcinomas, 93 (84.5%) were non-amplified, 12 (10.9%) were amplified and five (4.5%) were ISH-equivocal. All the HER2-amplified and two of ISH-equivocal cases (12.7%) corresponded to non-heterogeneous tumours, with highly significant differences evident in the average HER2/CEP17 ratio (P = 0.0002) and the proportion of cells with HER2 >6 copies (P < 0.0001) compared with heterogeneous lesions. NST grade 3 and HER2-amplified carcinomas average HER2/CEP17 ratio correlated with an increased number of cells with HER2/CEP17 >= 2.0 (P < 0.014). Triple-negative CEP17 polysomic carcinomas showed increased metastatic capacity (P = 0.003) compared with other tumour types.Conclusion: Non-heterogeneous HER2 IHC 2+ tumours tend to be HER2-amplified. Adding the percentage of cells with HER2 >6 copies to the average HER2/CEP17 ratio may facilitate assessment of amplification status in ISH-equivocal cases. The proportion of cells with HER2/CEP17 >= 2.0 contributes information concerning the actual average HER2/CEP17 ratio, depending on tumour type.
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