| 1. |
- Ask, Erik, et al.
(författare)
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Tractable and Reliable Registration of 2D Point Sets
- 2014
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Ingår i: Lecture Notes in Computer Science (Computer Vision - ECCV 2014, 13th European Conference, Zurich, Switzerland, September 6-12, 2014, Proceedings, Part I). - Cham : Springer International Publishing. - 0302-9743 .- 1611-3349. - 9783319105895 - 9783319105901 ; 8689, s. 393-406
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Konferensbidrag (refereegranskat)abstract
- This paper introduces two new methods of registering 2D point sets over rigid transformations when the registration error is based on a robust loss function. In contrast to previous work, our methods are guaranteed to compute the optimal transformation, and at the same time, the worst-case running times are bounded by a low-degree polynomial in the number of correspondences. In practical terms, this means that there is no need to resort to ad-hoc procedures such as random sampling or local descent methods that cannot guarantee the quality of their solutions. We have tested the methods in several different settings, in particular, a thorough evaluation on two benchmarks of microscopic images used for histologic analysis of prostate cancer has been performed. Compared to the state-of-the-art, our results show that the methods are both tractable and reliable despite the presence of a significant amount of outliers.
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| 2. |
- Krzyzanowska, Agnieszka, et al.
(författare)
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Quantitative Time-Resolved Fluorescence Imaging of Androgen Receptor and Prostate-Specific Antigen in Prostate Tissue Sections
- 2016
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Ingår i: Journal of Histochemistry and Cytochemistry. - : SAGE Publications. - 0022-1554 .- 1551-5044. ; 64:5, s. 311-322
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Tidskriftsartikel (refereegranskat)abstract
- Androgen receptor (AR) and prostate-specific antigen (PSA) are expressed in the prostate and are involved in prostate cancer (PCa). The aim of this study was to develop reliable protocols for reproducible quantification of AR and PSA in benign and malignant prostate tissue using time-resolved fluorescence (TRF) imaging techniques. AR and PSA were detected with TRF in tissue microarrays from 91 PCa patients. p63/ alpha-methylacyl-CoA racemase (AMACR) staining on consecutive sections was used to categorize tissue areas as benign or cancerous. Automated image analysis was used to quantify staining intensity. AR intensity was significantly higher in AMACR+ and lower in AMACR- cancer areas as compared with benign epithelium. The PSA intensity was significantly lower in cancer areas, particularly in AMACR- glands. The AR/PSA ratio varied significantly in the AMACR+ tumor cells as compared with benign glands. There was a trend of more rapid disease progression in patients with higher AR/PSA ratios in the AMACR- areas. This study demonstrates the feasibility of developing reproducible protocols for TRF imaging and automated image analysis to study the expression of AR and PSA in benign and malignant prostate. It also highlighted the differences in AR and PSA protein expression within AMACR- and AMACR+ cancer regions.
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| 3. |
- Larne, Olivia, et al.
(författare)
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miQ - a novel microRNA based diagnostic and prognostic tool for prostate cancer.
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 132:12, s. 2867-2875
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Tidskriftsartikel (refereegranskat)abstract
- Today, the majority of prostate tumours are detected at early stages with uncertain prognosis. Therefore, we set out to identify early predictive markers of prostate cancer with aggressive progression characteristics. We measured the expression of microRNAs (miRNA) using qRT-PCR in FFPE prostatic tissue samples from a Swedish cohort of 49 patients with prostate cancer and 25 without cancer and found eight of 14 preselected miRNAs to discriminate between the two groups. Subsequently four discriminatory miRNAs were combined to a quota, denoted the miRNA index quote (miQ); ((miR-96-5p x miR-183-5p)/(miR-145-5p x miR221-5p)). The advantage using a quote is increased discrimination, no need for house-keepings, and most important it may be an advantage considering the heterogeneity of the disease. miQ was found to successfully predict diagnosis (p<0.0001) with high accuracy (AUC=0.931) that was verified in an independent Dutch cohort and three external cohorts, and significantly outperforming PSA. Importantly, miQ also has prognostic power to predict aggressiveness of tumours (AUC=0.895), metastatic statues (AUC=0.827), and overall survival (p=0.0013, Wilcoxon test HR=6.5, median survival 2 versus 5 years), verified in the Dutch cohort. In this preliminary study we propose that miQ has potential to be used as a clinical tool for prostate cancer diagnosis and as a prognostic marker of disease progression. © 2012 Wiley Periodicals, Inc.
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| 4. |
- Lippolis, Giuseppe, et al.
(författare)
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A high-density tissue microarray from patients with clinically localized prostate cancer reveals ERG and TATI exclusivity in tumor cells.
- 2013
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 16:2, s. 145-150
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Tidskriftsartikel (refereegranskat)abstract
- Background:Prostate cancer (PCa) is characterized by high tumor heterogeneity. In 2005, the fusion between the androgen-regulated gene TMPRSS2 and members of the ETS family was discovered in prostate cancer. In particular, fusion of TMPRSS2 with ERG was found in approximately 50% of prostate cancers and considered as an early event in the onset of the disease. The prognostic value of this fusion is still contradictory. Bioinformatics showed that overexpression of SPINK1 gene in a subset of fusion-gene-negative prostate cancers was associated with a poor prognosis. In theory, overexpression of the tumor-associated trypsin inhibitor (TATI) protein encoded by SPINK1 in fusion-gene-negative tumor cells opens the way to selected treatments for genotypically different cases. However, their expression has never been assessed at the cellular level in the same tissue samples.Methods:As ERG expression has been shown to be a surrogate of fusion gene occurrence in prostate cancer, we have used double immunohistochemical staining to assess expression of ERG and TATI on a large tissue microarray comprising 4177 cases of localized prostate cancer.Results:We did not detect any co-expression of ERG and TATI in the same cancer cells, which confirms previous suggestions from in silico studies. ERG was associated with Gleason score (GS), surgical margins and pathological stage, but had no prognostic value in this cohort. TATI was weakly associated with pathological stage but had no significant association with outcome.Conclusions:We here provide a morphological basis for ERG and TATI exclusivity in prostate cancer cells. Future therapies should be based on a combination of different targets in order to eradicate tumor cells with gene fusions and cells expressing other tumor-associated antigens. Further studies are needed to understand why ERG and TATI are not co-expressed in the same prostatic tumor cells.Prostate Cancer and Prostatic Disease advance online publication, 5 March 2013; doi:10.1038/pcan.2013.7.
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| 5. |
- Lippolis, Giuseppe, et al.
(författare)
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Automatic registration of multi-modal microscopy images for integrative analysis of prostate tissue sections
- 2013
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13, s. 408-418
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Tidskriftsartikel (refereegranskat)abstract
- Background Prostate cancer is one of the leading causes of cancer related deaths. For diagnosis, predicting the outcome of the disease, and for assessing potential new biomarkers, pathologists and researchers routinely analyze histological samples. Morphological and molecular information may be integrated by aligning microscopic histological images in a multiplex fashion. This process is usually time-consuming and results in intra- and inter-user variability. The aim of this study is to investigate the feasibility of using modern image analysis methods for automated alignment of microscopic images from differently stained adjacent paraffin sections from prostatic tissue specimens. Methods Tissue samples, obtained from biopsy or radical prostatectomy, were sectioned and stained with either hematoxylin & eosin (H&E), immunohistochemistry for p63 and AMACR or Time Resolved Fluorescence (TRF) for androgen receptor (AR). Image pairs were aligned allowing for translation, rotation and scaling. The registration was performed automatically by first detecting landmarks in both images, using the scale invariant image transform (SIFT), followed by the well-known RANSAC protocol for finding point correspondences and finally aligned by Procrustes fit. The Registration results were evaluated using both visual and quantitative criteria as defined in the text. Results Three experiments were carried out. First, images of consecutive tissue sections stained with H&E and p63/AMACR were successfully aligned in 85 of 88 cases (96.6%). The failures occurred in 3 out of 13 cores with highly aggressive cancer (Gleason score ≥ 8). Second, TRF and H&E image pairs were aligned correctly in 103 out of 106 cases (97%). The third experiment considered the alignment of image pairs with the same staining (H&E) coming from a stack of 4 sections. The success rate for alignment dropped from 93.8% in adjacent sections to 22% for sections furthest away. Conclusions The proposed method is both reliable and fast and therefore well suited for automatic segmentation and analysis of specific areas of interest, combining morphological information with protein expression data from three consecutive tissue sections. Finally, the performance of the algorithm seems to be largely unaffected by the Gleason grade of the prostate tissue samples examined, at least up to Gleason score 7.
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| 6. |
- Lippolis, Giuseppe
(författare)
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Image analysis of prostate cancer tissue biomarkers
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer is the second most common cancer in men. In order to improve diagnosis and prognosis, new sensitive and specific biomarkers are needed. Tissue biomarkers carry expression and morphological information of the tissue where they are expressed. However their use is still limited by technological problems, lack of standardized procedures and inadequate interpretation. In this work we investigated a group of tissue biomarkers as well as new technologies and computerized approaches for consistent and reproducible analyses. We also tested an automated approach for performing Gleason grading. In order to validate previous in silico studies, we investigated the expression of ERG (as a surrogate marker of TMPRSS2:ERG gene fusion status) and TATI (encoded by SPINK1) proteins in a large TMA of localized prostate cancer patients. We observed a mutually exclusive expression pattern, further supporting the idea of tailored treatment for genotypically different cancers. In the second and third studies we introduce the use of image analysis for an integrated approach that uses Time Resolved Fluorescence Imaging on PSA and AR, immunofluorescence on cytokeratin as well as brightfield microscopy on H&E and p63/AMACR. The workflow includes the following automated steps: multi-modality image registration, identification of regions of interest, recognition of benign versus cancer areas and protein quantification. PSA seemed to decrease in cancer while AR increased in AMACR+ and decreased in AMACR- cancer tissue compared to benign. Finally, we developed a system based on SIFT features and BoW approach to automatically perform Gleason grading. The system was able to distinguish between grades with very high accuracy.
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| 7. |
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