Analytical Cellular Pathology - Volume 34, issue 5

Authors: Wax, Adam | Chalut, Kevin J.

Article Type: Review Article

Abstract: The study of intact, living cells using non-invasive optical spectroscopic methods offers the opportunity to assess cellular structure and organization in a way that is not possible with commonly used cell biology imaging techniques. We have developed a novel spectroscopic technique for diagnosing disease at the cellular level based on using low-coherence interferometry (LCI) to detect the angular distribution of scattered light. Angle-resolved LCI (a/LCI) combines the ability of LCI to isolate scattering from sub-surface tissue layers with the ability of light scattering spectroscopy to obtain structural information on sub-wavelength scales. In application to examining cellular structure, a/LCI enables quantitative …measurements of changes in the size and texture of cell nuclei. These quantitative measurements are characteristic of different pathological states. The capabilities of a/LCI were demonstrated using a clinical system that can be applied in endoscopic surveillance of esophageal tissue, producing high sensitivity and specificity for detecting dysplastic tissues in vivo. Experiments with in vitro cell samples also show the utility of a/LCI in observing structural changes due to environmental stimuli as well as detecting apoptosis due to chemotherapeutic agents. Show more

DOI: 10.3233/ACP-2011-0017

Citation: Analytical Cellular Pathology, vol. 34, no. 5, pp. 207-222, 2011

Authors: Coffman, Frederick | Hamid, Rachid | Cohen, Marion C. | Garippa, Ralph | Cohen, Stanley

Article Type: Research Article

Abstract: Despite significant differences in genetic profiles, cancer cells share common phenotypic properties, including membrane-associated changes that facilitate invasion and metastasis. The Corning Epic® optical biosensor was used to monitor dynamic mass rearrangements within and proximal to the cell membrane in tumor cell lines derived from cancers of the colon, bone, cervix, lung and breast. Data was collected in real time and required no exogenously added signaling moiety (signal-free technology). Cell lines displayed unique profiles over the time-courses: the time-courses all displayed initial signal increases to maximal values, but the rate of increase to those maxima and the value of …those maxima were distinct for each cell line. The rate of decline following the maxima also differed among cell lines. There were correlations between the signal maxima and the observed metastatic behavior of the cells in xenograft experiments; for most cell types the cells that were more highly metastatic in mice had lower time-course maxima values, however the reverse was seen in breast cancer cells. The unique profiles of these cell lines and the correlation of at least one profile characteristic with metastatic behavior demonstrate the potential utility of biophysical tumor cell profiling in the study of cancer biology. Show more

Keywords: biophysical measurement, mass redistribution, Epic\(^{\rm{®}}\) optical biosensor, tumor cells, metastasis

DOI: 10.3233/ACP-2011-0015

Citation: Analytical Cellular Pathology, vol. 34, no. 5, pp. 225-234, 2011

Authors: Torkaman, Atefeh | Charkari, Nasrollah Moghaddam | Aghaeipour, Mahnaz

Article Type: Research Article

Abstract: Hematological malignancies are the types of cancer that affect blood, bone marrow and lymph nodes. As these tissues are naturally connected through the immune system, a disease affecting one of them will often affect the others as well. The hematological malignancies include; Leukemia, Lymphoma, Multiple myeloma. Among them, leukemia is a serious malignancy that starts in blood tissues especially the bone marrow, where the blood is made. Researches show, leukemia is one of the common cancers in the world. So, the emphasis on diagnostic techniques and best treatments would be able to provide better prognosis and survival for patients. In …this paper, an automatic diagnosis recommender system for classifying leukemia based on cooperative game is presented. Through out this research, we analyze the flow cytometry data toward the classification of leukemia into eight classes. We work on real data set from different types of leukemia that have been collected at Iran Blood Transfusion Organization (IBTO). Generally, the data set contains 400 samples taken from human leukemic bone marrow. This study deals with cooperative game used for classification according to different weights assigned to the markers. The proposed method is versatile as there are no constraints to what the input or output represent. This means that it can be used to classify a population according to their contributions. In other words, it applies equally to other groups of data. The experimental results show the accuracy rate of 93.12%, for classification and compared to decision tree (C4.5) with (90.16%) in accuracy. The result demonstrates that cooperative game is very promising to be used directly for classification of leukemia as a part of Active Medical decision support system for interpretation of flow cytometry readout. This system could assist clinical hematologists to properly recognize different kinds of leukemia by preparing suggestions and this could improve the treatment of leukemic patients. Show more

Keywords: Game theory, cooperative game, shapley value, classification, leukemia

DOI: 10.3233/ACP-2011-0016

Citation: Analytical Cellular Pathology, vol. 34, no. 5, pp. 235-246, 2011

Authors: Edgerton, Mary E. | Chuang, Yao-Li | Macklin, Paul | Yang, Wei | Bearer, Elaine L. | Cristini, Vittorio

Article Type: Research Article

Abstract: We introduce a novel “mathematical pathology” approach, founded on a biophysical model, to identify robust patient-specific predictors of tumor growth useful in clinical practice to improve the accuracy of diagnosis/prognosis and intervention. In accordance with biological observations, our model simulates the diffusion-limited in situ tumors with a relatively short phase of fast initial growth, followed by a prolonged slow-growth phase where tumor size is constrained primarily by the relative weight of cell mitosis and death. The former phase may only last for a few months, so that at the time of diagnosis, we may assume that most tumors will have …entered the phase where their size is changing slowly. Based on this prediction, we hypothesize that the volume of breast with ducts affected by in situ tumors at the time of diagnosis will be closely approximated by a model-derived mathematical function based on the ratio of tumor cell proliferation-to-apoptosis indices and on the extent of diffusion of cell nutrients (diffusion penetration length), which can be measured from immunohistochemical and morphometric analysis of patient histopathology specimens without the need for multiple-time measurements. We tested this idea in a retrospective study of 17 patients by staining breast tumor specimens containing ductal carcinoma in situ for mitosis with Ki-67 and for apoptosis with cleaved caspase-3 and counting cells positive for each marker. We also determined diffusion penetration by measuring the thickness of viable rims of tumor cells within ducts. Using the ensuing ratios, we applied the model to determine a predicted surgical volume or tumor size. We then corroborated our hypothesis by comparing the predicted size of each tumor based on our model with the actual size of the pathological specimen after tumor excision (R2 = 0.74—0.88). In addition, for the 17 cases studied, both histological grade and mammography were not found to correlate with tumor size (R2 = 0.08—0.47). We conclude that our mathematical pathology approach yields a high degree of accuracy in predicting the size of tumors based on the mitotic/apoptotic index and on diffusion penetration. By obtaining these ratios at the time of initial biopsy, pathologists can employ our model to predict the size of the tumor and thereby inform surgeons how much tissue to remove (surgical volume). We discuss how results from the model have implications concerning the current debate on recommendations for screening mammography, while the model itself may contribute to better planning of breast conservation surgery. Show more

Keywords: DCIS, mathematical model, patient histology, IHC analysis, cell proliferation, cell death

DOI: 10.3233/ACP-2011-0019

Citation: Analytical Cellular Pathology, vol. 34, no. 5, pp. 247-263, 2011

Authors: Hipp, Jason | Cheng, Jerome | Daignault, Stephanie | Sica, Jefferey | Dugan, Michael C. | Lucas, David | Yagi, Yukako | Hewitt, Stephen | Balis, Ulysses J.

Article Type: Research Article

Abstract: Recently, with the advent of the 7th edition of the AJCC Cancer Staging manual, at least one set of criteria (e.g. breast) were modified to now require the measurement of maximal depth of stromal invasion. With the current manual interpretive morphological approaches typically employed by surgical pathologists to assess tumor extent, the specialty now potentially has stumbled upon a crossroads of practice, where the diagnostic criteria have exceeded the capabilities of our commonly available tools. While whole slide imaging (WSI) technology holds the potential to offer many improvements in clinical workflow over conventional slide microscopy including unambiguous utility for facilitating …quantitative diagnostic tasks with one important example being the determination of both linear dimension and surface area. However, the availability of histology data in digital form is of little utility if time-consuming and cumbersome manual workflow steps are necessarily imposed upon the pathologist in order to generate such measurements, especially as encountered with the complex and ill-defined shapes inherent to infiltrative tumors. In this communication, we demonstrate the utility of the recently described SIVQ algorithm to serve as the basis of a highly accurate, precise and semi-automated tool for direct surface area measurement of tumor infiltration from WSI data sets. By anticipating the current trend in cancer staging that emphasizes increasingly precise feature characterization, as witnessed by the recent publication of AJCC's 7th edition of the Cancer Staging Manual, this tool holds promise to will be of value to pathologists for clinical utility. Show more

Keywords: SIVQ, area calculation, WSI, digital slide

DOI: 10.3233/ACP-2011-0025

Citation: Analytical Cellular Pathology, vol. 34, no. 5, pp. 265-275, 2011