Assessment of chromosomal gains as compared to DNA content changes is more useful to detect dysplasia in Barrett's esophagus brush cytology specimens
Corresponding Author
Agnieszka M. Rygiel
Center for Experimental Molecular Medicine, Academic Medical Center, The Netherlands
Center for Experimental Molecular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ AmsterdamSearch for more papers by this authorFrancesca Milano
Center for Experimental Molecular Medicine, Academic Medical Center, The Netherlands
Search for more papers by this authorFebo J. ten Kate
Department of Pathology, Academic Medical Center, The Netherlands
Search for more papers by this authorJohn G. de Groot
Department of Pathology, Academic Medical Center, The Netherlands
Search for more papers by this authorMaikel P. Peppelenbosch
Department of Pathology, Academic Medical Center, The Netherlands
Department of Cell Biology, University Medical Center Groningen, University of Groningen, The Netherlands
Search for more papers by this authorJacques J. G. H. M. Bergman
Department of Gastroenterology and Hepatology, Academic Medical Center, The Netherlands
Search for more papers by this authorKauslillia K. Krishnadath
Department of Gastroenterology and Hepatology, Academic Medical Center, The Netherlands
Search for more papers by this authorCorresponding Author
Agnieszka M. Rygiel
Center for Experimental Molecular Medicine, Academic Medical Center, The Netherlands
Center for Experimental Molecular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ AmsterdamSearch for more papers by this authorFrancesca Milano
Center for Experimental Molecular Medicine, Academic Medical Center, The Netherlands
Search for more papers by this authorFebo J. ten Kate
Department of Pathology, Academic Medical Center, The Netherlands
Search for more papers by this authorJohn G. de Groot
Department of Pathology, Academic Medical Center, The Netherlands
Search for more papers by this authorMaikel P. Peppelenbosch
Department of Pathology, Academic Medical Center, The Netherlands
Department of Cell Biology, University Medical Center Groningen, University of Groningen, The Netherlands
Search for more papers by this authorJacques J. G. H. M. Bergman
Department of Gastroenterology and Hepatology, Academic Medical Center, The Netherlands
Search for more papers by this authorKauslillia K. Krishnadath
Department of Gastroenterology and Hepatology, Academic Medical Center, The Netherlands
Search for more papers by this authorAbstract
Abnormal DNA ploidy status has been suggested as a prognostic factor for Barrett's esophagus progression into esophageal adenocarcinoma (EAC). The aim of the study was to compare image cytometry DNA analysis (ICDA) and fluorescent in situ hybridization (FISH) in the assessment of DNA ploidy status in Barrett's esophagus (BE), and to determine the value of these abnormalities as an adjunct to conventional cytology in detection of dysplasia and EAC. Brush cytology specimens of 90 BE patients were examined using ICDA and FISH with peri-centromeric probes for chromosomes 7 and 17. The results of ICDA and FISH were compared with each other, and with dysplasia grade or EAC as determined by histology and cytology. FISH and ICDA detected abnormalities in 41% (37/90) and 22% (19/90) of the BE cases, respectively. Gains of chromosome 7 and/or 17 were present in 13% of nondysplasia cases, which further increased with dysplasia stage, while overall DNA content aneuploidy was detected predominantly in high grade dysplasia (HGD) and EAC. Using FISH results combined with cytology, we were able to identify IND/LGD (indefinite/ low grade dysplasia) with a sensitivity and specificity of 75 and 76%, respectively. FISH alone detected HGD/EAC with a high sensitivity and specificity of 85 and 84%, which was superior to that of cytology alone. Thus, FISH is more sensitive than ICDA to detect chromosomal abnormalities in BE brush cytology specimens. FISH detects chromosomal gains in early stages of BE and represents a valuable adjunct to conventional cytology to detect dysplasia or EAC. © 2008 Wiley-Liss, Inc.
REFERENCES
- Alanen KA,Lintu M,Joensuu H. 1998. Image cytometry of breast carcinomas that are DNA diploid by flow cytometry: Time to revise the concept of DNA diploidy? Anal Quant Cytol Histol 20: 178–186.
- Beilstein M,Silberg D. 2002. Cellular and molecular mechanisms responsible for progression of Barrett's metaplasia to esophageal carcinoma. Gastroenterol Clin North Am 31: 461–479, ix.
- Brankley SM,Wang KK,Harwood AR,Miller DV,Legator MS,Lutzke LS,Kipp BR,Morrison LE,Halling KC. 2006. The development of a fluorescence in situ hybridization assay for the detection of dysplasia and adenocarcinoma in Barrett's esophagus. J Mol Diagn 8: 260–267.
- Conio M,Blanchi S,Lapertosa G,Ferraris R,Sablich R,Marchi S,D'Onofrio V,Lacchin T,Iaquinto G,Missale G,Ravelli P,Cestari R,Benedetti G,Macri G,Fiocca R,Munizzi F,Filiberti R. 2003. Long-term endoscopic surveillance of patients with Barrett's esophagus. Incidence of dysplasia and adenocarcinoma: A prospective study. Am J Gastroenterol 98: 1931–1939.
- Curfman GD,Morrissey S,Drazen JM. 2006. Retraction: Sudbo J et al. DNA content as a prognostic marker in patients with oral leukoplakia. N Engl J Med2001; 344: 1270–8 and Sudbo J et al. The influence of resection and aneuploidy on mortality in oral leukoplakia.N Engl J Med2004; 350: 1405–13.N Engl J Med355:1927.
- Danesi DT,Spano M,Altavista P. 1993. Quality control study of the Italian group of cytometry on flow cytometry cellular DNA content measurements. Cytometry 14: 576–583.
- Doak SH,Jenkins GJ,Parry EM,D'souza FR,Griffiths AP,Toffazal N,Shah V,Baxter JN,Parry JM. 2003. Chromosome 4 hyperploidy represents an early genetic aberration in premalignant Barrett's oesophagus. Gut 52: 623–628.
- Duesberg P,Rausch C,Rasnick D,Hehlmann R. 1998. Genetic instability of cancer cells is proportional to their degree of aneuploidy. Proc Natl Acad Sci USA 95: 13692–13697.
- Fahmy M,Skacel M,Gramlich TL,Brainard JA,Rice TW,Goldblum JR,Connor JT,Casey G,Legator MS,Tubbs RR,Falk GW. 2004. Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus detected by fluorescence in situ hybridization of cytology specimens. Mod Pathol 17: 588–596.
- Falk GW. 2003. Cytology in Barrett's esophagus. Gastrointest Endosc Clin N Am 13: 335–348.
- Fang M,Lew E,Klein M,Sebo T,Su Y,Goyal R. 2004. DNA abnormalities as marker of risk for progression of Barrett's esophagus to adenocarcinoma: Image cytometric DNA analysis in formalin-fixed tissues. Am J Gastroenterol 99: 1887–1894.
- Fennerty MB,Sampliner RE,Way D,Riddell R,Steinbronn K,Garewal HS. 1989. Discordance between flow cytometric abnormalities and dysplasia in Barrett's esophagus. Gastroenterology 97: 815–820.
- Haggitt RC. 1992. Adenocarcinoma in Barrett's esophagus: A new epidemic? Hum Pathol 23: 475–476.
- Haroske G,Baak JP,Danielsen H,Giroud F,Gschwendtner A,Oberholzer M,Reith A,Spieler P,Bocking A. 2001. Fourth updated ESACP consensus report on diagnostic DNA image cytometry. Anal Cell Pathol 23: 89–95.
- Huang Q,Yu C,Klein M,Fang J,Goyal RK. 2005. DNA index determination with Automated Cellular Imaging System (ACIS) in Barrett's esophagus: Comparison with CAS. BMC Clin Pathol 5: 7.
- Jankowski JA,Wright NA,Meltzer SJ,Triadafilopoulos G,Geboes K,Casson AG,Kerr D,Young LS. 1999. Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Pathol 154: 965–973.
- Kyrgidis A,Kountouras J,Zavos C,Chatzopoulos D. 2005. New molecular concepts of Barrett's esophagus: Clinical implications and biomarkers. J Surg Res 125: 189–212.
- Maley CC,Galipeau PC,Li X,Sanchez CA,Paulson TG,Blount PL,Reid BJ. 2004. The combination of genetic instability and clonal expansion predicts progression to esophageal adenocarcinoma. Cancer Res 64: 7629–7633.
- Matzke MA,Mette MF,Kanno T,Matzke AJ. 2003. Does the intrinsic instability of aneuploid genomes have a causal role in cancer? Trends Genet 19: 253–256.
- Montgomery E,Goldblum JR,Greenson JK,Haber MM,Lamps LW,Lauwers GY,Lazenby AJ,Lewin DN,Robert ME,Washington K,Zahurak ML,Hart J. 2001. Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: A follow-up study based on 138 cases from a diagnostic variability study. Hum Pathol 32: 379–388.
- Persons DL,Takai K,Gibney DJ,Katzmann JA,Lieber MM,Jenkins RB. 1994. Comparison of fluorescence in situ hybridization with flow cytometry and static image analysis in ploidy analysis of paraffin-embedded prostate adenocarcinoma. Hum Pathol 25: 678–683.
- Pindur A,Chakraborty S,Welch DG,Wheeler TM. 1994. DNA ploidy measurements in prostate cancer: Differences between image analysis and flow cytometry and clinical implications. Prostate 25: 189–198.
- Rabinovitch PS,Longton G,Blount PL,Levine DS,Reid BJ. 2001. Predictors of progression in Barrett's esophagus III: Baseline flow cytometric variables. Am J Gastroenterol 96: 3071–3083.
- Reid BJ,Blount PL,Feng Z,Levine DS. 2000a. Optimizing endoscopic biopsy detection of early cancers in Barrett's high-grade dysplasia. Am J Gastroenterol 95: 3089–3096.
- Reid BJ,Blount PL,Rubin CE,Levine DS,Haggitt RC,Rabinovitch PS. 1992. Flow-cytometric and histological progression to malignancy in Barrett's esophagus: Prospective endoscopic surveillance of a cohort. Gastroenterology 102: 1212–1219.
- Reid BJ,Haggitt RC,Rubin CE,Roth G,Surawicz CM,Van Belle G,Lewin K,Weinstein WM,Antonioli DA,Goldman H. 1988. Observer variation in the diagnosis of dysplasia in Barrett's esophagus. Hum Pathol 19: 166–178.
- Reid BJ,Levine DS,Longton G,Blount PL,Rabinovitch PS. 2000b. Predictors of progression to cancer in Barrett's esophagus: Baseline histology and flow cytometry identify low- and high-risk patient subsets. Am J Gastroenterol 95: 1669–1676.
- Robey SS,Hamilton SR,Gupta PK,Erozan YS. 1988. Diagnostic value of cytopathology in Barrett esophagus and associated carcinoma. Am J Clin Pathol 89: 493–498.
- Rustgi AK. 1997. Biomarkers for malignancy in the columnar-lined esophagus. Gastroenterol Clin North Am 26: 599–606.
- Rygiel AM,van Baal JW,Milano F,Wang KK,ten Kate FJ,Fockens P,Rosmolen WD,Bergman JJ,Peppelenbosch MP,Krishnadath KK. 2007. Efficient automated assessment of genetic abnormalities detected by fluorescence in situ hybridization on brush cytology in a Barrett esophagus surveillance population. Cancer 109: 1980–1988.
- Saad RS,Mahood LK,Clary KM,Liu Y,Silverman JF,Raab SS. 2003. Role of cytology in the diagnosis of Barrett's esophagus and associated neoplasia. Diagn Cytopathol 29: 130–135.
- Spechler SJ. 2002. Clinical practice. Barrett's Esophagus. N Engl J Med 346: 836–842.
- Sudbo J,Kildal W,Risberg B,Koppang HS,Danielsen HE,Reith A. 2001. DNA content as a prognostic marker in patients with oral leukoplakia. N Engl J Med 344: 1270–1278.
- Susnik B,Poulin N,Phillips D,LeRiche J,Palcic B. 1995. Comparison of DNA measurement performed by flow and image cytometry of embedded breast tissue sections. Anal Quant Cytol Histol 17: 163–171.
- Tbakhi A,Totos G,Hauser-Kronberger C,Pettay J,Baunoch D,Hacker GW,Tubbs RR. 1998. Fixation conditions for DNA and RNA in situ hybridization: A reassessment of molecular morphology dogma. Am J Pathol 152: 35–41.
-
Teodori L,Gohde W,Persiani M,Ferrario F,Tirindelli Danesi D,Scarpignato C,Di Tondo U,Alo P,Capurso L.
1998.
DNA/protein flow cytometry as a predictive marker of malignancy in dysplasia-free Barrett's esophagus: Thirteen-year follow-up study on a cohort of patients.
Cytometry
34:
257–263.
10.1002/(SICI)1097-0320(19981215)34:6<257::AID-CYTO3>3.0.CO;2-S CAS PubMed Web of Science® Google Scholar
- Wang HH,Sovie S,Zeroogian JM,Spechler SJ,Goyal RK,Antonioli DA. 1997. Value of cytology in detecting intestinal metaplasia and associated dysplasia at the gastroesophageal junction. Hum Pathol 28: 465–471.
- Werner M,Mueller J,Walch A,Hofler H. 1999. The molecular pathology of Barrett's esophagus. Histol Histopathol 14: 553–559.