Pathology Image Analysis (PIA)
PEER-REVIEWED RESEARCH ARTICLES THAT UTILIZE ACIS
- University of Chicago users
- Tretiakova M, Turkyilmaz M, Grushko T, Kocherginsky M, Rubin C, Teh B, Yang XJ. Topoisomerase II alpha expression in Wilms tumors. J Clin Pathol. 2006 Dec;59(12):1272-7.
Evaluation of Immunostaining: Nuclear staining of TopoII and Ki-67 was quantified by using the Chromavision Automated Cellular Imaging System (Clarient Inc, Aliso Viejo, California, USA). The nuclear staining intensity was measured on the basis of three related colour, by setting colour-specific thresholds, to determine brown (positively stained) and blue (negative) nuclei in the outlined areas of interest, and to calculate the ratio (%) of positively stained nuclei to all nuclei (nuclear index). For each section, at least 10 representative regions were analysed and roughly 50 000 cells were counted.
- Dougherty U, Sehdev A, Cerda S, Mustafi R, Little N, Yuan W, Jagadeeswaran S, Chumsangsri A, Delgado J, Tretiakova M, Joseph L, Hart J, Cohen EE, Aluri L, Fichera A, Bissonnette M. Epidermal growth factor receptor controls flat dysplastic aberrant crypt foci development and colon cancer progression in the rat azoxymethane model. Clin Cancer Res. 2008 Apr 15;14(8):2253-62.
Immunostaining quantitation. We detected transcription factor expression and Ki67 by nuclear staining, apoptosis by cleaved caspase-3 expression, and blood vessels by nestin-1 staining. Staining levels were quantified by an automated cellular imaging system (Clarient) with settings optimized for nuclear staining, vessel detection, or apoptosis from five representative fields per slide. Proliferation was measured by the percentage of nuclei positive for Ki67 and apoptosis was expressed as the percentage of cells positive for cleaved caspase-3. Microvessel densities were assessed as the vessel area normalized to total tissue area. Nuclear expression for FosB, c-Jun, and C/EBPh were quantified as the percentage of positive nuclei as previously described (22). Color-specific thresholds were used to determine brown (positive) and blue (negative) nuclei within the outlined areas of interest and to calculate the ratio of positively stained nuclei to all nuclei and expressed as a percentage (nuclear index). At least five fields per tumor and three tumors per group (50,000 cells/condition) were scanned for quantitation.
- Leong H, Mathur PS, Greene GL. Inhibition of mammary tumorigenesis in the C3(1)/SV40 mouse model by green tea. Breast Cancer Res Treat. 2008 Feb;107(3):359-69.
The slides were then counterstained with hematoxylin, dehydrated, and permanently mounted. Scoring of positively stained cells was performed using the Automated Cellular Imaging System (ACIS, ChromaVision, San Juan Capistrano, CA). Briefly, stained sections were scanned and acquired using an ACIS imaging/microscopy system. Ki67 and VEGF expression were evaluated as the percentage of positively stained cells in ductal and lobular units and adjacent stroma. Microvessels were defined as CD31-stained clusters or single cells with or without a lumen.
- Jiang Z, Wu CL, Woda BA, Iczkowski KA, Chu PG, Tretiakova MS, Young RH, Weiss LM, Blute RD Jr, Brendler CB, Krausz T, Xu JC, Rock KL, Amin MB, Yang XJ. Alpha-methylacyl-CoA racemase: a multi-institutional study of a new prostate cancer marker. Histopathology. 2004 Sep;45(3):218-25.
Quantitative analysis of the Immunostaining: The Automated Cellular Imaging System (ACIS; ChromaVision Medical System Inc., San Juan Capistrano, CA, USA) and Ariol Imaging System (Applied Imaging Corp., Santa Clara, CA, USA) were used to evaluate the immunostaining in prostatic adenocarcinoma compared with adjacent benign prostatic tissue in the same section. Positive staining is calculated by applying two thresholds with one recognizing blue background (haematoxylin stained) cells and another recognizing brown positive cells. The percentage of positivity is the area detected by the brown threshold divided by the sum of the area detected by the brown and blue thresholds. The intensity is calculated by masking out all areas not selected by the brown threshold and calculating the integrated optical density of brown within the remaining area. This value is divided by the area in pixels of the brown mask to calculate an average intensity of a selected area. The values from 60 areas of benign prostatic epithelium and 60 areas of malignant prostatic epithelium were obtained and analysed by using the ChromaVision ACIS. The values from 60 areas including benign prostatic tissue (n = 24), prostatic adenocarcinoma (n = 20) and high-grade PIN (n = 16) were analysed by using the Ariol Imaging System.
- Jagadeeswaran R, Surawska H, Krishnaswamy S, Janamanchi V, Mackinnon AC, Seiwert TY, Loganathan S, Kanteti R, Reichman T, Nallasura V, Schwartz S, Faoro L, Wang YC, Girard L, Tretiakova MS, Ahmed S, Zumba O, Soulii L, Bindokas VP, Szeto LL, Gordon GJ, Bueno R, Sugarbaker D, Lingen MW, Sattler M, Krausz T, Vigneswaran W, Natarajan V, Minna J, Vokes EE, Ferguson MK, Husain AN, Salgia R. Paxillin is a target for somatic mutations in lung cancer: implications for cell growth and invasion. Cancer Res. 2008 Jan 1;68(1):132-42.
- Faoro L, Loganathan S, Westerhoff M, Modi R, Husain AN, Tretiakova M, Seiwert T, Kindler HL, Vokes EE, Salgia R. Protein kinase C beta (PKCβ) in malignant pleural mesothelioma. 2008, In press.
- Kort E, Farber L, Tretiakova M, Petillo D, Furge K, Yang XJ, Cornelius A, Teh BT. The E2F3-Oncomir-1 axis is activated in Wilms` tumors. Cancer Res. 2008 Jun 1;68(11):4034-8.
- Gao ZH, Tretiakova MS, Liu WH, Gong C, Farris PD, Hart J. Association of E-cadherin, matrix metalloproteinases, and tissue inhibitors of metalloproteinases with the progression and metastasis of hepatocellular carcinoma. Mod Pathol. 2006 Apr;19(4):533-40.
- Sawada K, Radjabi AR, Shinomiya N, Kistner E, Kenny H, Becker AR, Turkyilmaz MA, Salgia R, Yamada SD, Vande Woude GF, Tretiakova MS, Lengyel E. c-Met overexpression is a prognostic factor in ovarian cancer and an effective target for inhibition of peritoneal dissemination and invasion. Cancer Res. 2007 Feb 15;67(4):1670-9.
- Tretiakova M, Turkyilmaz M, Grushko T, Kocherginsky M, Rubin C, Teh B, Yang XJ. Topoisomerase II alpha expression in Wilms tumors. J Clin Pathol. 2006 Dec;59(12):1272-7.
- Outside users
- 2003. Ayala G, Wang D, Wulf G, Frolov A, Li R, Sowadski J, Wheeler T, Lu K, Bao L. The Prolyl Isomerase Pin1 Is a Novel Prognostic Marker in Human Prostate Cancer. Cancer Res 63:6244-6251.
- 2000. Bauer KD, Torre Bueno, J, Diel IJ, Hawes D, Decker WJ, Priddy C, Bossy B, Ludmann S, Yamamoto K, Masih AS, Espinoza FP, and Harrington DS. Reliable and sensitive analysis of occult bone marrow metastases using automated cellular imaging. Clin Cancer Res 6:3552-3559.
- 2005. Becker S, Becker-Pergola G, Fehm T, Emig R, Wallwiener D, Solomayer E. Image Analysis Systems for the Detection of Disseminated Breast Cancer Cells on Bone-Marrow Cytospins. J Clin Lab Anal 19:115-119.
- 2001. Birner P, Ritzi M, Musahl C, Knippers R, Gerdes J, Voigtlander T, Budka H, Hainfellner J. Immunohistochemical Detection of Cell Growth Fraction in Formalin-Fixed and Paraffin-Embedded Murine Tissue. Am J Pathol 158:1991-1996.
- 2004. Bloom K and Harrington D. Enhanced Accuracy and Reliability of HER-2/neu Immunohistochemical Scoring Using Digital Microscopy. Am J Clin Pathol 121:620-630.
- 2004. Brown RE, Lun M, Prichard JW, Blasick TM, Zhang PL. Morphoproteomic and Pharmacoproteomic Correlates in Hormone-Receptor-Negative Breast Carcinoma Cell Lines. Ann Clin Lab Sci 34:251-62.
- 2004. Charpin C, Dales Jean-Philippe, Garcia Stephane, Carpentier Severine, Djemli Amina, Andrac Lucile, Lavaut Marie-Noelle, Allasia Claude, Bonnier Pascal. Tumor Neoangiogenesis by CD31 and CD105 Expression Evaluation in Breast Carcinoma Tissue Microarrays. Clin Cancer Res 10:5815-5819.
- 2004. Choesmel V, Pierga JY, Nos C, Vincent-Salomon A, Sigal-Zafrani B, Thiery JP, Blin N. Enrichment methods to detect bone marrow micrometastases in breast carcinoma patients: clinical relevance. Breast Cancer Res 6:R556-570.
- 2004. Faith D, Isaacs W, Morgan J, Fedor H, Hicks J, Mangold L, Walsh P, Partin A, Platz E, Luo J, DeMarzo A. Trefoil Factor 3 Overexpression in Prostatic Carcinoma: Prognostic Importance Using Tissue Microarrays. Prostate 61:215-227.
- 2004. Grupka NL, Lear-Kaul KC, Kleinschmidt-DeMasters BK, Singh M. Epidermal growth factor receptor status in breast cancer metastases to the central nervous system. Comparison with HER-2/neu status. Arch Pathol Lab Med 128:974-979.
- 2003. Hilbe W, Gachter A, Duba HC, Dirnhofer S, Eisterer W, Schmid T, Mildner A, Bodner J, Woll E. Comparison of Automated Cellular Imaging System and Manual Microscopy for Immunohistochemically Stained Cryostat Sections of Lung Cancer Specimens Applying p53, ki-67 and p120. Oncol Rep 10:15-20.
- 2005. Huang Q, Yu C, Klein M, Fang J, Goyal RK. DNA index determination with Automated Cellular Imaging System (ACIS) in Barrett's esophagus: Comparison with CAS 200. BMC Clin Pathol 5:in press.
- 2005. Kowal-Vern A, Webster SD, Rasmasubban S, Casey L, Bauer K, Latenser BA, Rubin DB. Circulating Endothelial Cell Levels Correlate with Proinflammatory Cytokine Increase in the Acute Phase of Thermal Injury. J Burn Care Rehabil 26:422-429.
- 2004. Luftner D, Henschke P, Kafka A, Anagnostopoulos I, Wiechen K, Geppert R, Stein H, Wernecke KD, Kreienberg R, Possinger K. Discordant Results Obtained for Different Methods of HER-2/neu Testing in Breast Cancer –a Question of Standardization, Automation and Timing. Int J Biol Markers 19:1-13.
- 2002. Maitra A, Ashfaq R, Gunn C, Rahman A, Yeo C, Sohn T, Cameron J, Hruban R, Wilentz R. Cyclooxygenase 2 Expression in Pancreatic Adenocarcinoma and Pancreatic Intraepithelial Neoplasia. Am J Clin Pathol 118:194-201.
- 2003. Melsheimer P, Kaul S, Dobeck S, Bastert G. Immunocytochemical Detection of Human Papillomavirus High Risk Type L1 Capsid Proteins in LSIL and HSIL as Compared with Detection of HPV L1 DNA. Acta Cytol 47:124-128.
- 2005. Nunez MI, Rosen DG, Ludes-Meyers JH, Abba MC, Kil H, Page R, Klein-Szanto AJ, Godwin AK, Liu J, Mills GB, Aldaz CM. WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome. BMC Cancer 5:64-73.
- 2005. Nunez MI, Ludes-Meyers J, Abba MC, Kil H, Abbey NW, Page RE, Sahin A, Klein-Szanto AJ, Aldaz CM. Frequent loss of WWOX expression in breast cancer: correlation with estrogen receptor status. Breast Cancer Res Treat 89:99-105.
- 2003. Pierga J-Y, Bonneton C, Magdelenat H, Vincent-Salomon A, Nos C, Pouillart P, Thiery J-P. Clinical significance of proliferative potential of occult metastatic cells in bone marrow of patients with breast cancer. Br J Cancer 89:539-545.
- 2004. Pierga J-Y, Bonneton C, Vincent-Salomon A, de Cremoux P, Nos C, Blin N, Pouillart P, Thiery JP, Magdelanet H. Clinical significance of immunocytochemical detection tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients. Clin Cancer Res 10:1392-1400.
- 2004. Pollack A, DeSilvio M, Khor LY, Li R, Al-Saleem TI, Hammond ME, Venkatesan V, Lawton CA, Roach III M, Shipley WU, Hanks GE, Sandler HM. Ki-67 Staining is a Strong Predictor of Distant Metastasis and Mortality for Men with Prostate Cancer Treated with Radiotherapy Plus Androgen Deprivation: Radiation Therapy Oncology Group Trial 92-02. J Clin Oncol 22:2133-2140.
- 2002. Shukla D, Veeramachaneni R, Abreo F, Nordberg M. HER-2/neu Status: Comparison of Quantitative Immunohistochemistry by Automated Cellular Imaging and Fluorescence In Situ Hybridization. Pathol Case Rev 7:75-80.
- 2002. Sun W, Zhang P, Herrera G. p53 Protein and Ki-67 Overexpression in Urothelial Dysplasia of Bladder. Appl Immunohistochem Mol Morphol 10:327-331.
- 2006. Tawfik OW, Kimler BF, Davis M, Donahue JK, Persons DL, Fan F, Hagemeister S, Thomas P, Connor C, Jewell W, Fabian CJ. Comparison of immunohistochemistry by automated cellular imaging system (ACIS) versus fluorescence in-situ hybridization in the evaluation of HER-2/neu expression in primary breast carcinoma. Histopathology 48: 258–267.
- 2005. Trousdale MD, Zhu Z, Stevenson D, Schechter JE, Ritter T, Mircheff AK. Expression of TNF inhibitor gene in the lacrimal gland promotes recovery of tear production and tear stability and reduced immunopathology in rabbits with induced autoimmune dacryoadenitis. J Autoimmune Dis 2:6-14.
- 2004. van Gijssel H, Schild L, Watt D, Roth M, Wang G, Dawsey S, Albert P, Qiao Y, Taylor P, Dong Z, Poirier M. Polycyclic aromatic hydrocarbon-DNA adducts determined by semiquantitative immunohistochemistry in human esophageal biopsies taken in 1985. Mutat Res 547:55-62.
- 2002. van Gijssel HE, Divi RL, Olivero OA, Roth MJ, Wang GQ, Dawsey SM, Albert PS, Qiao YL, Taylor PR, Dong ZW, Schrager JA, Kleiner DE, Poirier MC. Semiquantitation of polycyclic aromatic hydrocarbon-DNA adducts in human esophagus by immunohistochemistry and the automated cellular imaging system. Cancer Epidemiol Biomarkers Prev 11:1622-1629.
- 2004. Vesoulis Z, Rajappannair L, Define L, Beach J, Vesoulis Z, Schnell B, Myers S. Quantitative Image Analysis of Estrogen Receptors in Breast Fine Needle Aspiration Biopsies. Anal Quant Cytol Histol 26:323-330.
- 2001. Wang S, Saboorian MH, Frenkel EP, Haley BB, Siddiqui MT, Gokaslan S, Wians FH Jr, Hynan L, Ashfaq R. Assessment of HER-2/neu status in breast cancer. Automated Cellular Imaging System (ACIS)-assisted quantitation of immunohistochemical assay achieves high accuracy in comparison with fluorescence in situ hybridization assay as the standard. Am J Clin Pathol 116:495-503.
- 2002. Wang S, Saboorian MH, Frenkel E, Haley B, Siddiqui M, Gokaslan S, Hynan L, Ashfaq R. Aneusomy 17 in Breast Cancer: Its Role in HER-2/neu Protein Expression and Implication for Clinical Assessment of Her-2/neu Status. Mod Pathol 15:137-145.
- 2003. Weaver D, Krag D, Manna E, Ashikaga T, Harlow S, Bauer K. Comparison of Pathologist-Detected and Automated Computer-Assisted Image Analysis Detected Sentinel Lymph Node Micrometastases in Breast Cancer. Mod Pathol 16:1159-1163.
- 2002. Witzig T, Bossy B, Kimlinger T, Roche P, Ingle J, Grant C, Donohue J, Suman V, Harrington D, Torre-Bueno J, Bauer K. Detection of Circulating Cytokeratin-positive Cells in the Blood of Breast Cancer Patients Using Immunomagnetic Enrichment and Digital Microsopy. Clin Cancer Res 8:1085-1091.
- 2003. Zhu Z, Stevenson D, Schechter J, Mircheff A, Atkinson R, Trousdale M Lacrimal Histopathology and Ocular Surface Disease in a Rabbit Model of Autoimmune Dacryoadenitis. Cornea 22:25-32.
- 2003. Zhu Z, Stevenson D, Schechter J, Mircheff A, Crow R, Atkinson R, Ritter T, Bose S, Trousdale M Tumor Necrosis Factor Inhibitor Gene Expression Suppresses Lacrimal Gland Immunopathology in a Rabbit Model of Autoimmune Dacryoadenitis. Cornea 22:343-351.









