Analytical Cellular Pathology - Volume 35, issue 4

Authors: Badea, Alexandra | Johnson, G. Allan

Article Type: Review Article

DOI: 10.3233/ACP-2011-0050

Citation: Analytical Cellular Pathology, vol. 35, no. 4, pp. 205-227, 2012

Authors: Isikman, Serhan O. | Greenbaum, Alon | Lee, Myungjun | Bishara, Waheb | Mudanyali, Onur | Su, Ting-Wei | Ozcan, Aydogan

Article Type: Review Article

Abstract: The recent revolution in digital technologies and information processing methods present important opportunities to transform the way optical imaging is performed, particularly toward improving the throughput of microscopes while at the same time reducing their relative cost and complexity. Lensfree computational microscopy is rapidly emerging toward this end, and by discarding lenses and other bulky optical components of conventional imaging systems, and relying on digital computation instead, it can achieve both reflection and transmission mode microscopy over a large field-of-view within compact, cost-effective and mechanically robust architectures. Such high throughput and miniaturized imaging devices can provide a complementary toolset for …telemedicine applications and point-of-care diagnostics by facilitating complex and critical tasks such as cytometry and microscopic analysis of e.g., blood smears, Pap tests and tissue samples. In this article, the basics of these lensfree microscopy modalities will be reviewed, and their clinically relevant applications will be discussed. Show more

Keywords: Lensfree imaging, on-chip microscopy, lensless microscopy, telemedicine, digital holography, high-throughput imaging, wide field-of-view microscopy, global health, digital pathology

DOI: 10.3233/ACP-2012-0057

Citation: Analytical Cellular Pathology, vol. 35, no. 4, pp. 229-247, 2012

Authors: Hipp, Jason | Monaco, James | Kunju, L. Priya | Cheng, Jerome | Yagi, Yukako | Rodriguez-Canales, Jaime | Emmert-Buck, Michael R. | Hewitt, Stephen | Feldman, Michael D. | Tomaszewski, John E. | Toner, Mehmet | Tompkins, Ronald G. | Flotte, Thomas | Lucas, David | Gilbertson, John R. | Madabhushi, Anant | Balis, Ulysses

Article Type: Research Article

Abstract: Introduction: The advent of digital slides offers new opportunities within the practice of pathology such as the use of image analysis techniques to facilitate computer aided diagnosis (CAD) solutions. Use of CAD holds promise to enable new levels of decision support and allow for additional layers of quality assurance and consistency in rendered diagnoses. However, the development and testing of prostate cancer CAD solutions requires a ground truth map of the cancer to enable the generation of receiver operator characteristic (ROC) curves. This requires a pathologist to annotate, or paint, each of the malignant glands in prostate cancer with an …image editor software - a time consuming and exhaustive process. Recently, two CAD algorithms have been described: probabilistic pairwise Markov models (PPMM) and spatially-invariant vector quantization (SIVQ). Briefly, SIVQ operates as a highly sensitive and specific pattern matching algorithm, making it optimal for the identification of any epithelial morphology, whereas PPMM operates as a highly sensitive detector of malignant perturbations in glandular lumenal architecture. Methods: By recapitulating algorithmically how a pathologist reviews prostate tissue sections, we created an algorithmic cascade of PPMM and SIVQ algorithms as previously described by Doyle el al. [1] where PPMM identifies the glands with abnormal lumenal architecture, and this area is then screened by SIVQ to identify the epithelium. Results: The performance of this algorithm cascade was assessed qualitatively (with the use of heatmaps) and quantitatively (with the use of ROC curves) and demonstrates greater performance in the identification of malignant prostatic epithelium. Conclusion: This ability to semi-autonomously paint nearly all the malignant epithelium of prostate cancer has immediate applications to future prostate cancer CAD development as a validated ground truth generator. In addition, such an approach has potential applications as a pre-screening/quality assurance tool. Show more

Keywords: Pathology informatics, whole slide imaging, computer aided diagnosis, SIVQ, PPMM, digital imaging, prostate cancer, cancer

DOI: 10.3233/ACP-2012-0054

Citation: Analytical Cellular Pathology, vol. 35, no. 4, pp. 251-265, 2012

Authors: Ouchani, F. | Devy, J. | Rusciani, A. | Helesbeux, J.J. | Salesse, S. | Letinois, I. | Gras-Billart, D. | Duca, L. | Duval, O. | Martiny, L. | Charpentier, E.

Article Type: Research Article

Abstract: Background: Leukemic cell adhesion to proteins of the bone marrow microenvironment provides signals which control morphology, motility and cell survival. We described herein the ability of ethoxyfagaronine (etxfag), a soluble synthetic derivative of fagaronine, to prevent leukemic cell adhesion to fibronectin peptide (FN/V). Methods: Phosphorylation of fak and pyk2 were evaluated by immunoblotting. Labelled proteins were localized by confocal microscopy. PI 3-kinase activity was evaluated by in vitro kinase assay. Results: Subtoxic concentration of etxfag reduced L1210 cell adhesion to FN/V dependently of β1 integrin engagement. Etxfag impaired FN-dependent formation of β1 clustering without modifying β1 expression at the cell …membrane. This was accompanied by a decrease of focal adhesion number, a diminution of fak and pyk2 phosphorylation at Tyr-576, Tyr-861 and Tyr-579, respectively leading to their dissociations from β1 integrin and inhibition of PI 3-kinase activity. Etxfag also induced a cell retraction accompanied by a redistribution of phosphorylated fak and pyk2 in the perinuclear region and lipid raft relocalization. Conclusion: Through its anti-adhesive potential, etxfag, combined with conventional cytotoxic drugs could be potentially designed as a new anti-leukemic drug. Show more

Keywords: Adhesion, ethoxyfagaronine, integrin, focal adhesion kinases, acute leukemia

DOI: 10.3233/ACP-2012-0055

Citation: Analytical Cellular Pathology, vol. 35, no. 4, pp. 267-284, 2012

Authors: Zhu, Yimin | Xiao, Xingyuan | Dong, Lairong | Liu, Zhiming

Article Type: Research Article

Abstract: MicroRNAs are small noncoding RNA molecules that control expression of target genes. Our previous studies show that let-7a decreased in gastric carcinoma and that up-regulation of let-7a by gene augmentation inhibited gastric carcinoma cell growth both in vitro and in vivo, whereas it remains largely unclear as to how let-7a affects tumor growth. In this study, proteins associated with the function of let-7a were detected by high throughout screening. The cell line of SGC-7901 stablely overexpressing let-7a was successfully established by gene cloning. Two-dimensional gel electrophoresis (2-DEy was used to separate the total proteins of SGC-7901/let-7a, SGC-7901/EV and SGC-7901, and …PDQuest software was applied to analyze 2-DE images. Ten different protein spots were identified by MALDI-TOF-MS, and they may be the proteins associated with let-7a function. The overexpressed proteins included Antioxidant protein 2, Insulin–like growth factor binding protein 2, Protein disulfide isomerase A2, C-1-tetrahydrofolate synthase, Cyclin-dependent kinase inhibitor1 (CDKN1) and Rho–GTPase activating protein 4. The underexpressed proteins consisted of S-phase kinase-associated protein 2 (Spk2), Platelet membrane glycoprotein, Fibronectin and Cks1 protein. Furthermore, the different expression levels of the partial proteins (CDKN1, Spk2 and Fibronectin) were confirmed by western blot analysis. The data suggest that these differential proteins are involved in a novel let-7a signal pathway and these findings provide the basis to investigate the functional mechanisms of let-7a in gastric carcinoma. Show more

Keywords: Proteomics, miRNA, gastric carcinoma

DOI: 10.3233/ACP-2012-0063

Citation: Analytical Cellular Pathology, vol. 35, no. 4, pp. 285-295, 2012

Authors: Styczeń, Magdalena | Szpor, Joanna | Demczuk, Sergiusz | Okoń, Krzysztof

Article Type: Research Article

Abstract: Background: Marginal zone lymphomas are indolent B-cell lymphomas associated with autoimmunity and chronic inflammation. The two most frequent variants are mucosa associated lymphoid tissues marginal zone lymphomas and splenic marginal zone lymphomas. The aim of the study was to determine if it is possible to classify splenic and gastric lymphomas according to karyometric features. Methods: The material consisted of 16 splenic and 14 gastric lymphomas. The measurements were done with the AnalySIS image analysis system. In each case at least 100 nuclei were selected, and 19 different geometric parameters were measured. Results: On statistical analysis, the nuclei of splenic and …gastric lymphomas showed differences in most parameters, but significant overlap of the values was present. Neural networks were trained and used for classification of the data. By this method, the nuclei were properly classified with a sensitivity of 0.75 and specificity of 0.71. In addition, in all the cases the majority of the nuclei were properly classified, thus allowing correct classification of all the cases into “splenic” or “gastric”. Conclusion: These results support the view that mucosa-associated lymphoid tissue lymphomas and splenic marginal-zone lymphomas are separate entities. Show more

Keywords: Marginal zone lymphoma, image analysis, karyometry, neural network, classification

DOI: 10.3233/ACP-2012-0064

Citation: Analytical Cellular Pathology, vol. 35, no. 4, pp. 297-303, 2012

Authors: Nielsen, Birgitte | Albregtsen, Fritz | Kildal, Wanja | Abeler, Vera M. | Kristensen, Gunnar B. | Danielsen, Håvard E.

Article Type: Research Article

Abstract: Background: Nuclear texture analysis gives information about the spatial arrangement of the pixel gray levels in a digitized microscopic nuclear image, providing texture features that may be used as quantitative tools for prognosis of human cancer. The aim of the study was to evaluate the prognostic value of adaptive nuclear texture features in early stage ovarian cancer. Methods: 246 cases of early stage ovarian cancer were included in the analysis. Isolated nuclei (monolayers) were prepared from 50 μm tissue sections and stained with Feulgen-Schiff. Local gray level entropy was measured within small windows of each nuclear image and stored in …gray level entropy matrices. A compact set of adaptive features was computed from these matrices. Results: Univariate Kaplan-Meier analysis showed significantly better relapse-free survival (p < 0.001) for patients with low adaptive feature values compared to patients with high adaptive feature values. The 10-year relapse-free survival was about 78% for patients with low feature values and about 52% for patients with high feature values. Adaptive features were found to be of independent prognostic significance for relapse-free survival in a multivariate analysis. Conclusion: Adaptive nuclear texture features from entropy matrices contain prognostic information and are of independent prognostic significance for relapse-free survival in early stage ovarian cancer. Show more

Keywords: Adaptive texture features, early stage ovarian cancer, nuclear texture analysis, pattern classification, prognostic marker

DOI: 10.3233/ACP-2012-0065

Citation: Analytical Cellular Pathology, vol. 35, no. 4, pp. 305-314, 2012