Objective: The Bethesda System (TBS) of uterine cervical cytology is a classification method that can improve accuracy in management and it includes descriptions on adequate specimens, human papillomavirus (HPV) involvement and estimated lesions. However, the judgment of atypical squamous cells of undetermined significance (ASC-US) using TBS features complicated diagnostic criteria and poor reproducibility due to the definition of ASC-US. Of patients diagnosed with ASC-US in the initial cytology, cervical intraepithelial neoplasia (CIN)1-2 cases positive for high-risk HPV (CIN+) and benign cases in histology negative for high-risk HPV (B-) were selected for discriminant analysis based on Mahalanobis distance, in order to improve the accuracy of the ASC-US diagnosis. Study Design: ASC-US cases featuring koilocytosis with little nuclear atypia (koilocytosis) and squamous epithelial cells with nuclear atypia (SC with atypia), morphologically diagnosed with liquid-based cytology specimens prepared using ThinPrep were included. The nuclei of koilocytosis cases (CIN+, 8 cases, and B-, 10 cases) and SC with atypia (CIN+, 19 cases, and B-, 15 cases) were three-dimensionally analyzed to conduct a discriminant analysis based on Mahalanobis distance. Results: Discrimination rates were 78.9% for CIN+ and 66.7% for B- in koilocytosis, and 50.7% for CIN+ and 72.1% for B- in SC with atypia. Conclusion: The present method allows the objective analysis of nuclear chromatin, providing effective cytology regarding CIN+ in koilocytosis and B- in SC with atypia of ASC-US cases.

Sherman ME, Dasgupta A, Schiffman M, Nayar R, Solomon D: The Bethesda Interobserver Reproducibility Study (BIRST): a web-based assessment of the Bethesda 2001 System for classifying cervical cytology. Cancer 2007;111:15-25.
Washiya K, Abe I, Ambo J, Iwai M, Okusawa E, Asanuma K, Watanabe J: Cytological analysis of atypical squamous epithelial cells of undetermined significance using the world wide web. Acta Cytol 2011;55:319-326.
Stoler MH, Schiffman M, ALTS Group: Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA 2001;285:1500-1505.
Washiya K, Konno T, Ishii A, Tokairin T, Ono I: Evaluation of the urine cytodiagnosis using simple method of measuring nucleus brightness histogram. J Jpn Soc Clin Cytol 2008;28:154-155.
Washiya K, Kanno T, Tone K, Kojima K, Kijima H, Watanabe J: Three-dimensional nuclear luminance analysis in well-differentiated adenocarcinoma of the lung. Acta Cytol 2011;55:350-356.
Washiya K, Noro T, Narumi K, Kurose A, Yoshioka H, Watanabe J: Usefulness of discriminant analysis using nuclear three-dimensional analysis in atypical cells prepared from bronchial brushing cytology cases that are cytologically challenging. Acta Cytol 2012;56:297-303.
Washiya K, Narumi K, Noro T, Hamakawa S, Furuta N, Yoshioka H, Watanabe J: Discriminant analysis of malignant mesothelioma and reactive mesothelium using three-dimensional nuclear estimation. Acta Cytol 2012;56:189-195.
Origoni M, Carminati G, Sideri M, Clementi M, Rolla S, Candiani M: ‘Low-grade positivity' of HPV viral load after atypical squamous cells of undetermined significance (ASC-US) cytology identifies women at low-risk for cervical intraepithelial neoplasia grade 2 and 3. Eur J Gynaecol Oncol 2012;33:261-264.
Goto Y, Shinjo K, Kondo Y, Shen L, Toyota M, Suzuki H, et al: Epigenetic profiles distinguish malignant pleural mesothelioma from lung adenocarcinoma. Cancer Res 2009;69:9073-9082.
Ohm JE, Baylin SB: Stem cell chromatin patterns: an instructive mechanism for DNA hypermethylation? Cell Cycle 2007;6:1040-1043.
Kanai Y, Hirohashi S: Alterations of DNA methylation associated with abnormalities of DNA methyltransferases in human cancers during transition from a precancerous to a malignant state. Carcinogenesis 2007;28:2434-2442.
Kondo Y, Kanai Y, Sakamoto M, Mizokami M, Ueda R, Hirohashi S: Genetic instability and aberrant DNA methylation in chronic hepatitis and cirrhosis - a comprehensive study of loss of heterozygosity and microsatellite instability at 39 loci and DNA hypermethylation on 8 CpG islands in microdissected specimens from patients with hepatocellular carcinoma. Hepatology 2000;32:970-979.
Kanai Y, Hirohashi S: Alterations of DNA methylation associated with abnormalities of DNA methyltransferases in human cancers during transition from a precancerous to a malignant state. Carcinogenesis 2007;28:2434-2442.
Arai E, Kanai Y, Ushijima S, Fujimoto H, Mukai K, Hirohashi S: Regional DNA hypermethylation and DNA methyltransferase (DNMT) 1 protein overexpression in both renal tumors and corresponding nontumorous renal tissues. Int J Cancer 2006;119:288-296.
Arai E, Ushijima S, Fujimoto H, Hosoda F, Shibata T, Kondo T, Yokoi S, Imoto I, Inazawa J, Hirohashi S, Kanai Y: Genome-wide DNA methylation profiles in both precancerous conditions and clear cell renal cell carcinomas are correlated with malignant potential and patient outcome. Carcinogenesis 2009;30:214-221.
Friedrich MG, Weisenberger DJ, Cheng JC, Chandrasoma S, Siegmund KD, Gonzalgo ML, Toma MI, Huland H, Yoo C, Tsai YC, Nichols PW, Bochner BH, Jones PA, Liang G: Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients. Clin Cancer Res 2004;10:7457-7465.
Apostolidou S, Hadwin R, Burnell M, Jones A, Baff D, Pyndiah N, Mould T, Jacobs IJ, Beddows S, Kocjan G, Widschwendter M: DNA methylation analysis in liquid-based cytology for cervical cancer screening. Int J Cancer 2009;125:2995-3002.
Noguchi M, Furuya S, Takeuchi T, Hirohashi S: Modified formalin and methanol fixation methods for molecular biological and morphological analyses. Pathol Int 1997;47:685-691.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.