Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Gastroenterology
Published in: BMC Gastroenterology 1/2010

Open Access 01-12-2010 | Research article

Chromosomal imbalances are uncommon in chagasic megaesophagus

Authors: Marilanda F Bellini, Antonio J Manzato, Ana E Silva, Marileila Varella-Garcia

Published in: BMC Gastroenterology | Issue 1/2010

Login to get access

Abstract

Background

Chagas' disease is a human tropical parasitic illness and a subset of the chronic patients develop megaesophagus or megacolon. The esophagus dilation is known as chagasic megaesophagus (CM) and one of the severe late consequences of CM is the increased risk for esophageal carcinoma (ESCC). Based on the association between CM and ESCC, we investigated whether genes frequently showing unbalanced copy numbers in ESCC were altered in CM by fluorescence in situ (FISH) technology.

Methods

A total of 50 formalin-fixed, paraffin-embedded esophageal mucosa specimens (40 from Chagas megaesophagus-CM, and 10 normal esophageal mucosa-NM) were analyzed. DNA FISH probes were tested for FHIT, TP63, PIK3CA, EGFR, FGFR1, MYC, CDKN2A, YES1 and NCOA3 genes, and centromeric sequences from chromosomes 3, 7 and 9.

Results

No differences between superficial and basal layers of the epithelial mucosa were found, except for loss of copy number of EGFR in the esophageal basal layer of CM group. Mean copy number of CDKN2A and CEP9 and frequency of nuclei with loss of PIK3CA were significantly different in the CM group compared with normal mucosa and marginal levels of deletions in TP63, FHIT, PIK3CA, EGFR, CDKN2A, YES and gains at PIK3CA, TP63, FGFR1, MYC, CDNK2A and NCOA3 were detected in few CM cases, mainly with dilation grades III and IV. All changes occurred at very low levels.

Conclusions

Genomic imbalances common in esophageal carcinomas are not present in chagasic megaesophagus suggesting that these features will not be effective markers for risk assessment of ESCC in patients with chagasic megaesophagus.
Appendix
Available only for authorised users
Literature
1.
2.
Moncayo A, Silveira CA: Current epidemiological trends for Chagas disease in Latin America and future challenges in epidemiology, surveillance and health policy. Mem Inst Oswaldo Cruz. 2009, 104 (I): 17-30.PubMed
3.
Kraichely RE, Farrugia G: Achalasia: physiology and etiopathogenesis. Dis Esophagus. 2006, 19: 213-223. 10.1111/j.1442-2050.2006.00569.x.CrossRefPubMed
4.
Bektas A, Yasa MH, Kuzu I, Dogan I, Unal S, Ormeci N: Flow Cytometric DNA analysis and immunohistochemical p53, PCNA and histopathologic study in primary achalasia: preliminary results. Hepatogastroenterology. 2001, 48: 408-412.PubMed
5.
Brücher BLDM, Stein HJ, Bartels H, Feussner H, Siewert JR: Achalasia and esophageal cancer: incidence, prevalence and prognosis. World J Surg. 2001, 25: 745-749. 10.1007/s00268-001-0026-3.CrossRefPubMed
6.
Gockel I, Kammerer P, Brieger J, Heinrich UR, Mann WJ, Bittinger F, Eckardt VF, Junginger T: Image cytometric DNA analysis of mucosal biopsies in patients with primary achalasia. World J Gastroenterol. 2006, 21: 3020-3025.CrossRef
7.
Chino O, Kijima H, Shimada H, Nishi T, Tanaka H, Oshiba G, Kise Y, Kajiwara H, Tsuchida T, Tanaka M, Tajima T, Makuuchi H: Clinicopathological studies of esophageal carcinoma in achalasia: analysis of carcinogenesis using histological and immunohistochemical procedures. Anticancer Res. 2000, 20: 3717-3722.PubMed
8.
9.
10.
Kuwano H, Kato H, Miyazaki T, Fukuchi M, Masuda N, Nakajima M, Fukai Y, Sohda M, Kimura H, Faried A: Genetic alterations in esophageal cancer. Surg Today. 2005, 35: 7-18. 10.1007/s00595-004-2885-3.CrossRefPubMed
11.
D'Amico TA: Molecular biologic staging of esophageal cancer. Thorac Surg Clin. 2006, 16 (Suppl 4): 31-327.
12.
Pack SD, Karkera JD, Zhuang Z, Pak ED, Balan KV, Hwu P, Park WS, Pham T, Ault DO, Glaser M, Liotta L, Detera-Wadleigh SD, Wadleigh RG: Molecular cytogenetic fingerprinting of esophageal squamous cell carcinoma by comparative genomic hybridization reveals a consistent pattern of chromosomal alterations. Genes Chromosomes Cancer. 1999, 25 (2): 160-168. 10.1002/(SICI)1098-2264(199906)25:2<160::AID-GCC12>3.0.CO;2-U.CrossRefPubMed
13.
Yen CC, Chen YJ, Chen JT, Hsia JY, Chen PM, Liu JH, Fan FS, Chiou TJ, Wang WS, Lin CH: Comparative genomic hybridization of esophageal squamous cell carcinoma: correlations between chromosomal aberrations and disease progression/prognosis. Cancer. 2001, 92 (11): 2769-2777. 10.1002/1097-0142(20011201)92:11<2769::AID-CNCR10118>3.0.CO;2-M.CrossRefPubMed
14.
Ishizuka T, Tanabe C, Sakamoto H, Aoyagi K, Maekawa M, Matsukura N, Tokunaga A, Tajiri T, Yoshida T, Terada M, Sasaki H: Gene amplification profiling of esophageal squamous cell carcinomas by DNA array CGH. Biochem Biophys Res Commun. 2002, 296 (1): 152-5. 10.1016/S0006-291X(02)00836-7.CrossRefPubMed
15.
Nakakuki K, Imoto I, Pimkhaokham A, Fukuda Y, Shimada Y, Imamura M, Amagasa T, Inazawa J: Novel targets for the 18p11.3 amplification frequently observed in esophageal squamous cell carcinomas. Carcinogenesis. 2002, 23 (1): 19-24. 10.1093/carcin/23.1.19.CrossRefPubMed
16.
Arai H, Ueno T, Tangoku A, Yoshino S, Abe T, Kawauchi S, Oga A, Furuya T, Oka M, Sasaki K: Detection of amplified oncogenes by genome DNA microarrays in human primary esophageal squamous cell carcinoma: comparison with conventional comparative genomic hybridization analysis. Cancer Genet Cytogenet. 2003, 146 (1): 16-21. 10.1016/S0165-4608(03)00106-7.CrossRefPubMed
17.
Shiomi H, Sugihara H, Kamitani S, Tokugawa T, Tsubosa Y, Okada K, Tamura H, Tani T, Kodama M, Hattori T: Cytogenetic heterogeneity and progression of esophageal squamous cell carcinoma. Cancer Genet Cytogenet. 2003, 147 (1): 50-61. 10.1016/S0165-4608(03)00159-6.CrossRefPubMed
18.
Yen CC, Chen YJ, Pan CC, Lu KH, Chen PC, Hsia JY, Chen JT, Wu YC, Hsu WH, Wang LS, Huang MH, Huang BS, Hu CP, Chen PM, Lin CH: Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma: TP63 is amplified in early carcinogenesis but down-regulated as disease progressed. World J Gastroenterol. 2005, 11 (9): 1267-1272.CrossRefPubMedPubMedCentral
19.
Wang LD, Qin YR, Fan ZM, Kwong D, Guan XY, Tsao GS, Sham J, Li JL, Feng XS: Comparative genomic hybridization: comparison between esophageal squamous cell carcinoma and gastric cardia adenocarcinoma from a high-incidence area for both cancers in Henan, northern China. Dis Esophagus. 2006, 19 (6): 459-67. 10.1111/j.1442-2050.2006.00620.x.CrossRefPubMed
20.
de Rezende J, Lauar KM, de Oliveira A: Clinical and radiological aspects of aperistalsis of the esophagus. Rev Bras Gastroenterol. 1960, 12: 247-262.PubMed
21.
Pekarsky Y, Zanesi N, Palamarchuk A, Huebner K, Croce CM: FHIT: from gene discovery to cancer treatment and prevention. Lancet Oncol. 2002, 3: 748-54. 10.1016/S1470-2045(02)00931-2.CrossRefPubMed
22.
Chen PL, Cheng YW, Chiang CC, Tseng SH, Chau PS, Tsai YY: Hypermethylation of the p16 gene promoter in pterygia and its association with the expression of DNA methyltransferase 3b. Molecular Vision. 2006, 12: 1411-1416.PubMed
23.
24.
Pelucchi C, Gallus S, Garavello W, Bosetti C, La Vecchia C: Alcohol and tobacco use, and cancer risk for upper aerodigestive tract and liver. Eur J Cancer Prev. 2008, 17 (4): 340-344. 10.1097/CEJ.0b013e3282f75e91.CrossRefPubMed
25.
Mori T, Miura K, Aoki T, Nishihira T, Mori S, Nakamura Y: Frequent somatic mutation of the MTS1/CDK4I (multiple tumor suppressor/cyclin-dependent kinase 4 inhibitor) gene in esophageal squamous cell carcinoma. Cancer Res. 1994, 54: 3396-3397.PubMed
26.
Nuovo G, Plaia TW, Belinsky SA, Baylin SB, Herman JG: In situ detection of the hypermethylation-induced inactivation of the p16 gene as an early event in oncogenesis. PNAS. 1999, 96 (22): 12754-12759. 10.1073/pnas.96.22.12754.CrossRefPubMedPubMedCentral
27.
Kato H, Yoshikawa M, Fukai Y, Tajima K, Masuda N, Tsukada K, Kuwano H, Nakajima T: An immunohistochemical study of p16, pRb, p21 and p53 proteins in human esophageal cancers. Anticancer Res. 2000, 20: 345-349.PubMed
28.
Chang MS, Lee HS, Lee BL, Kim YT, Lee JS, Kim WH: Differential protein expression between esophageal squamous cell carcinoma and dysplasia, and prognostic significance of protein markers. Pathol Res Pract. 2005, 201 (Suppl 6): 417-425. 10.1016/j.prp.2005.04.005.CrossRefPubMed
29.
Huang H, Wang LF, Tian HM, Liu Y, Li M, Qu P, Wang WR, Zhang W: Expression of retinoic acid receptor-beta mRNA and p16, p53, Ki67 proteins in esophageal carcinoma and its precursor lesions. Zhonghua Zhong Liu Za Zhi. 2005, 27 (3): 152-5.PubMed
30.
Fujiwara S, Noguchi T, Takeno S, Kimura Y, Fumoto S, Kawahara K: Hypermethylation of p16 gene promoter correlates with loss of p16 expression that results in poorer prognosis in esophageal squamous cell carcinomas. Dis Esophagus. 2008, 21: 125-131. 10.1111/j.1442-2050.2007.00735.x.CrossRefPubMed
31.
Chen J, Guo L, Peiffer DA, Zhou L, Chan OT, Bibikova M, Wickham-Garcia E, Lu SH, Zhan Q, Wang-Rodriguez J, Jiang W, Fan JB: Genomic profiling of 766 cancer-related genes in archived esophageal normal and carcinoma tissues. Int J Cancer. 2008, 122 (10): 2249-54. 10.1002/ijc.23397.CrossRefPubMed
32.
Kim YT, Park JY, Jeon YK, Park SJ, Song JY, Kang CH, Sung SW, Kim JH: Aberrant promoter CpG island hypermethylation of the adenomatosis polyposis coli gene can serve as a good prognostic factor by affecting lymph node metastasis in squamous cell carcinoma of the esophagus. Dis Esophagus. 2009, 22 (2): 143-50. 10.1111/j.1442-2050.2008.00862.x.CrossRefPubMed
33.
Bellini MF, Leite KRM, Cury PM, Silva AE: p53, p16 and Fhit proteins expressions in chronic esophagitis and chagas disease. Anticancer Res. 2008, 28 (Suppl 6B): 3793-3799.PubMed
34.
Manoel-Caetano FS, Silveira AFP, Silva AE: Gene mutations in esophageal mucosa of Chagas disease patients. Anticancer Res. 2009, 29 (Suppl 4): 1243-1247.
35.
Manoel-Caetano F, da S, Borim AA, Caetano A, Cury PM, Silva AE: Cytogenetic alterations in chagasic achalasia compared to esophageal carcinoma. Cancer Genet Cytogenet. 2004, 149 (1): 17-22. 10.1016/S0165-4608(03)00274-7.CrossRef
36.
Druck T, Hadaczek P, Fu TB, Ohta M, Siprashvili Z, Baffa R, Negrini M, Kastury K, Veronese ML, Rosen D, Rothstein J, McCue P, Cotticelli MG, Inoue H, Croce CM, Huebner K: Structure and expression of the human FHIT gene in normal and tumor cells. Cancer Res. 1997, 57: 504-512.PubMed
37.
Mori M, Mimori K, Shiraishi T, Alder H, Inoue H, Tanaka Y, Sugimachi K, Huebner K, Croce CM: Altered expression of Fhit in carcinoma and precarcinomatous lesions of the esophagus. Cancer Res. 2000, 60: 1177-1182.PubMed
38.
Kuroki T, Trapasso F, Yendamuri S, Matsuyama A, Alder H, Mori M, Croce CM: Allele loss and promoter hypermethylation of VLH, RAR-beta, RASSF1A, and FHIT tumor suppressor genes on chromosome 3p in esophageal squamous cell carcinoma. Cancer Res. 2003, 63: 3724-3728.PubMed
39.
Roth MJ, Abnet CC, Hu N, Wang QH, Wei WQ, Green L, D'Alelio M, Qiao YL, Dawsey SM, Taylor PR, Woodson K: p16, MGMT, RARbeta2, CLDN3, CRBP and MT1G gene methylation in esohageal squamous cell carcinoma and its precursor lesions. Oncol Rep. 2006, 15 (6): 1591-1597.PubMed
40.
Yen CC, Chen YJ, Lu KH, Hsia JY, Chen JT, Hu CP, Chen PM, Liu JH, Chiou TJ, Wang WS, Yang MH, Chao TC, Lin CH: Genotypic analysis of esophageal squamous cell carcinoma by molecular cytogenetics and real-time quantitative polymerase chain reaction. Int J Oncol. 2003, 23 (4): 871-881.PubMed
41.
Yang YL, Chu JY, Luo ML, Wu YP, Zhang Y, Feng YB, Shi ZZ, Xu X, Han YL, Cai Y, Dong JT, Zhan QM, Wu M, Wang MR: Amplification of PRKCI, located in 3q26, is associated with lymph node metastasis in esophageal squamous cell carcinoma. Genes Chromosomes Cancer. 2008, 47 (2): 127-136. 10.1002/gcc.20514.CrossRefPubMed
42.
43.
Hibi K, Trink B, Patturajan M, Westra WH, Caballero OL, Hill DE, Ratovitski EA, Jen J, Sidransky D: AIS is an oncogene amplified in squamous cell carcinoma. Proc Natl Acad Sci USA. 2000, 97 (Suppl 10): 5462-5467. 10.1073/pnas.97.10.5462.CrossRefPubMedPubMedCentral
44.
Hu H, Xia SH, Li AD, Xu X, Cai Y, Han YL, Wei F, Chen BS, Huang XP, Han YS, Zhang JW, Zhang X, Wu M, Wang MR: Elevated expression of p63 protein in human esophageal squamous cell carcinomas. Int J Cancer. 2002, 102: 580-583. 10.1002/ijc.10739.CrossRefPubMed
45.
Sunpaweravong P, Sunpaweravong S, Puttawibul P, Mitarnun W, Zeng C, Barón AE, Franklin W, Said S, Varella-Garcia M: Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol. 2005, 131 (2): 111-119. 10.1007/s00432-004-0610-7.CrossRefPubMed
46.
Hanawa M, Suzuki S, Dobashi Y, Yamane T, Kono K, Enomoto N, Ooi A: EGFR protein overexpression and gene amplification in squamous cell carcinomas of the esophagus. Int J Cancer. 2006, 118 (Suppl 5): 1173-1180. 10.1002/ijc.21454.CrossRefPubMed
47.
Sugiura K, Ozawa S, Kitagawa Y, Ueda M, Kitajima M: Co-expression of aFGF and FGFR-1 is predictive of a poor prognosis in patients with esophageal squamous cell carcinoma. Oncol Rep. 2007, 17 (3): 557-564.PubMed
48.
Adhikary S, Eilers M: Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol. 2005, 6: 635-645. 10.1038/nrm1703.CrossRefPubMed
49.
Fujita Y, Sakakura C, Shimomura K, Nakanishi M, Yasuoka R, Aragane H, Hagiwara A, Abe T, Inazawa J, Yamagishi H: Chromosome arm 20q gains and other genomic alterations in esophageal squamous cell carcinoma, as analyzed by comparative genomic hybridization and fluorescence in situ hybridization. Hepatogastroenterol. 2003, 50 (Suppl 54): 1857-1863.
50.
Xu FP, Xie D, Wen JM, Wu HX, Liu YD, Bi J, Lv ZL, Zeng YX, Guan XY: SRC-3/AIB1 protein and gene amplification levels in human esophageal squamous cell carcinomas. Cancer Lett. 2007, 245 (1-2): 69-74. 10.1016/j.canlet.2005.12.030.CrossRefPubMed
51.
Xu FP, Liu YH, Zhuang HG, Li L, Luo XL, Wen JM: Role of AIB1 gene in development of esophageal squamous cell carcinoma and its clinicopathologic significance. Zhonghua Bing Li Xue Za Zhi. 2008, 37 (4): 250-254.PubMed
52.
Pajecki D, Zilberstein B, dos Santos MA, Ubriaco JA, Quintanilha AG, Cecconello I, Gama-Rodrigues J: Megaesophagus Microbiota: A Qualitative and Quantitative Analysis. Journal of Gastrointestinal Surgery. 2002, 6: 723-729. 10.1016/S1091-255X(02)00028-8.CrossRefPubMed
53.
Lehman MB, Clark SB, Ormsby AH, Rice TW, Richter JE, Goldblum JR: Squamous mucosal alterations in esophagectomy specimens from patients with end-stage achalasia. Am J Surg Pathol. 2001, 25: 1413-1418. 10.1097/00000478-200111000-00009.CrossRefPubMed
Metadata
Title
Chromosomal imbalances are uncommon in chagasic megaesophagus
Authors
Marilanda F Bellini
Antonio J Manzato
Ana E Silva
Marileila Varella-Garcia
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2010
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/1471-230X-10-20

Other articles of this Issue 1/2010

BMC Gastroenterology 1/2010 Go to the issue

Research article

Lack of Guanylate Cyclase C results in increased mortality in mice following liver injury

Research article

Carbon monoxide-Releasing Molecule-2 (CORM-2) attenuates acute hepatic ischemia reperfusion injury in rats

Research article

Reproductive life disorders in Italian celiac women. A case-control study

Research article

African-American inflammatory bowel disease in a Southern U.S. health center

Case report

Acute retroperitoneal bleeding due to inferior mesenteric artery aneurysm: Case report

Research article

Differences in bleeding behavior after endoscopic band ligation: a retrospective analysis
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits