| 1. |
- Wärnberg, Fredrik, et al.
(författare)
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Quality aspects of the tissue microarray technique in a population-based cohort with ductal carcinoma in situ of the breast
- 2008
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 53:6, s. 642-649
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Tissue microarray (TMA) is an efficient technique for analysis of molecular markers. Prospectively collected samples have been reported to give excellent concordance between TMA data and corresponding whole-sections. The aim was to evaluate the usefulness of TMA in a population-based cohort of 213 women with ductal carcinoma in situ of the breast (DCIS). METHODS AND RESULTS: We studied immunohistochemical HER2, oestrogen (ER) and progesterone (PR) receptor status. The prognostic impact was similar for all markers comparing whole sections and TMAs. The proportion of positive tumours was similar regarding HER2 and ER, whereas PR tumours were more frequently positive in the TMAs (P = 0.007). The concordance was 80% (kappa value 0.63) between original sections and TMAs. The proportion of successfully analysed tumours was 70%. Smaller tumours had a lower ratio (P < 0.0001) and a larger proportion of mismatched results (P = 0.05). CONCLUSIONS: Retrospective analyses of tumours from cohorts with long-term follow-up are indispensable. We have shown that the TMA technique is a useful tool for high-throughput analysis of DCIS. However, our study has pinpointed some technical hazards within a population-based cohort, including many small lesions and the poor condition of some donor blocks. Mismatched results may be due to tumour heterogeneity.
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| 2. |
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| 3. |
- Ahlin, Cecilia, et al.
(författare)
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Ki67 and cyclin A as prognostic factors in early breast cancer : What are the optimal cut-off values?
- 2007
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 51:4, s. 491-498
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To find the optimal cut-off values for cyclin A and Ki67 in early breast cancer tumours and to evaluate their prognostic values. METHODS AND RESULTS: Tissue microarray (TMA) slides were constructed from 570 T1-4 N0-1 M0 breast cancer tumours. The TMA slides were stained for cyclin A and Ki67 using immunohistochemistry with commercial antibodies. To investigate the optimal cut-off values for cyclin A, Ki67 average and maximum values the material was split into two parts at cut-offs defined by dividing it into deciles. For each cut-off value the relative risk (RR) for metastasis-free survival (MFS) and overall survival (OS) was calculated comparing patients with high versus low cyclin A or Ki67 expression. When using a cut-off value around the seventh decile, cyclin A and Ki67 score correlated with the highest RR ratio for MFS in the chemotherapy-naïve subgroup. Among patients having received adjuvant chemotherapy, no statistically significant differences in MFS or OS were found. CONCLUSIONS: The optimal cut-off value for cyclin A average is 8% and for cyclin A maximum value 11%; for Ki67 the corresponding values are 15% and 22%. Additional studies are needed to verify these results.
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| 4. |
- Glimelius, Ingrid, et al.
(författare)
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Tissue microarray and digital image analysis : a methodological study with special reference to the microenvironment in Hodgkin lymphoma
- 2012
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 61:1, s. 26-32
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Cancer research has moved from solely investigating the tumour cells to also including analysis of the tumour microenvironment; however, the methods utilized have not been evaluated for this change. The aim of this study was to compare tissue microarrays (TMA) to whole tissue sections (WS) with regard to cells in the tumour microenvironment. Manual evaluation and digital image analyses (DIA) were utilized and also compared.Methods and results: TMA slides from 117 Hodgkin lymphoma patients were immunostained for forkhead box protein 3 (FoxP3) [identifying regulatory T cells (T(reg) )], and 39 corresponding WS were also analysed. Manual evaluation and DIA were utilized for all patients on both the TMA and the WS. A correlation coefficient of 0.83 was obtained for the proportion of T(reg) in TMA versus WS using manual evaluation and a correlation coefficient of 0.77 with DIA. T(reg) counts using manual evaluation correlated in turn with DIA, with a coefficient of 0.79 for the 117 TMA sections and 0.65 for the 39 WS.Conclusion: Because a high correlation was observed between TMA and WS, TMA can be utilized when evaluating cells in the tumour microenvironment. DIA appears to provide a reliable measurement method, provided that manual control of the tumour slides is conducted.
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| 5. |
- Mattsson, Johanna Sofia Margareta, et al.
(författare)
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Consistent mutation status within histologically heterogeneous lung cancer lesions
- 2012
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 61:4, s. 744-748
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Activating epidermal growth factor receptor (EGFR) and KRAS mutations characterize molecular subgroups of non-small-cell lung cancer (NSCLC) with a strong predictive value for response to EGFR inhibitor therapy. However, the temporal occurrence and clonal stability of these mutations during the course of cancer progression are debated. The aim of this study was to characterize the presence of EGFR and KRAS mutations in histologically different areas of primary NSCLC lesions. Methods and results: Formalin-fixed paraffin-embedded cancer specimens from six cases with EGFR mutations and five cases with KRAS mutations were selected from a pool of primary resected NSCLC patients. From each tumour, three morphologically distinct areas were manually microdissected and analysed for the presence of mutations. The results demonstrated consistent EGFR and KRAS mutation status in the different histological areas of all primary tumours. Conclusions: The results support the concept that activating EGFR and KRAS mutations are oncogenic events that are consistently present throughout the primary tumour independently of histological heterogeneity. Thus, for molecular diagnostics, any part of the tumour is likely to be representative for EGFR and KRAS mutation testing.
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| 6. |
- Richardsen, E., et al.
(författare)
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The prognostic impact of M-CSF, CSF-1 receptor, CD68 and CD3 in prostatic carcinoma
- 2008
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 53:1, s. 30-38
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Macrophage colony-stimulating factor (M-CSF) binds to colony-stimulating factor-1 receptor (CSF-1R) and stimulates proliferation and differentiation of monocytes, macrophages and their bone marrow progenitors. M-CSF, CSF-1R, the macrophage marker CD68, and the pan T-lymphocyte marker CD3 are increased in many human cancers. Their prognostic importance in primary prostatic carcinoma has not been fully delineated. The aim was to compare the expression of M-CSF, CSF-1R, CD68 and CD3 in metastatic and non-metastatic prostatic cancer. Methods and results: Digital video analysis of tumour cell areas and tumour stromal areas was performed in 59 cancer specimens: 32 patients with metastases and 27 patients without metastases. Expression of M-CSF and CSF-1R was recorded as 0 (negative immunoreactivity), 1 (weak), 2 (moderate) or 3 (strong reactivity). Macrophages (CD68) and T lymphocytes (CD3) were detected as proportions of moderately or strongly immunoreactive cells. Patients with metastatic primary cancers showed higher expression of M-CSF (P < 0.0001, P = 0.005), CSF-1R (both P < 0.0001) and CD3 (P = 0.007, P < 0.0001) in both tumour cell areas and tumour stromal areas, compared with the non-metastatic cancers. Conclusions: This study suggests that expression of M-CSF, CSF-1R and CD3 is a significant prognostic factor in primary prostatic cancers by predicting the development of metastases.
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| 7. |
- Soini, Ylermi, et al.
(författare)
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Claudins 1, 11 and twist in meningiomas
- 2010
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 56:6, s. 821-824
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Willen, R., et al.
(författare)
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Intestinal spirochaetosis
- 2006
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 49:6, s. 658-9
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Tidskriftsartikel (refereegranskat)
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| 9. |
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| 10. |
- 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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