Skip to main content

Advertisement

SpringerLink
Log in

Role of E-cadherin gene in gall bladder cancer and its precursor lesions

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The aim was to investigate the genomic instability in the E-cadherin (CDH1) gene and to correlate it with its protein expression in gall bladder cancer (GBC) and in other gall bladder (GB) diseases viz. chronic cholecystitis (CC), xantho-granulomatous cholecystitis (XGC), and normal GB to explicate its role in GBC tumorigenesis. Microsatellite instability (MSI) and loss of heterozygosity (LOH) in CDH1 were studied using D16S421, D16S496, D16S503, D16S512, D16S2624, and D16S3021 microsatellite markers and D2S123 (2p16), D2S382 (2q24), D6S292 (6q21–23), D7S480 (7q31), and D17S796 (17p13.1–3) were used to investigate genomic instability at 2p, 2q, 6q, 7q, and 17p loci in 40 GBC, 50 CC, 34 XGC, and 15 normal GB cases. Immunohistochemistry was carried out to analyze the E-cadherin and p53 protein expression. Overall LOH in CDH1 and other markers was high in GBC and XGC as compared to CC; however, it did not correlate with its protein expression in GBC cases. Loss of E-cadherin expression was high in GBC (67%), while majority of the CC (94%) and XGC (91%) cases retained positive E-cadherin expression. Overexpression of p53 was high in GBC (43%) whereas CC, XGC, normal GB cases were negative for p53 overexpression. None of the normal GB cases showed genomic instability at any of the markers. High LOH in CDH1 and other chromosomal loci in GBC indicated that the genomic instability followed a GBC>XGC>CC trend during the process of neoplastic transformation in GB, highlighting the fact that CC might act as a precursor lesion of GBC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kapoor VK, McMichael AJ (2003) Gallbladder cancer: an ‘Indian’ disease. Natl Med J India 16:209–213

    CAS  PubMed  Google Scholar 

  2. Dhir V, Mohandas KM (1999) Epidemiology of digestive tract cancers in India IV. Gall bladder and pancreas. Indian J Gastroenterol 18:24–28

    CAS  PubMed  Google Scholar 

  3. Silk YN, Douglass HO Jr, Nava HR et al (1989) Carcinoma of the gallbladder. The Roswell Park experience. Ann Surg 210:751–757

    Article  CAS  PubMed  Google Scholar 

  4. Berx G, Staes K, van Hengel J et al (1995) Cloning and characterization of the human invasion suppressor gene E-cadherin (E-cadherin). Genomics 26:281–289

    Article  CAS  PubMed  Google Scholar 

  5. Puhalla H, Herberger B, Soleiman A et al (2005) E-cadherin and β-catenin expression in normal, inflamed and cancerous gallbladder tissue. Anticancer Res 6:4249–4254

    Google Scholar 

  6. Fleming ID, Phillips JL, Menck HR et al (1997) The National Cancer Data Base report on recent hospital cancer program progress toward complete American Joint Committee on Cancer/TNM staging. Cancer 80:2305–2310

    Article  CAS  PubMed  Google Scholar 

  7. Boland CR, Thibodeau SN, Hamilton SR et al (1998) A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257

    CAS  PubMed  Google Scholar 

  8. Chaube A, Tewari M, Garbyal RS et al (2006) Preliminary study of p53 and c-erbB-2 expression in gallbladder cancer in Indian patients. BMC Cancer 6:126

    Article  PubMed  Google Scholar 

  9. Misra S, Chaturvedi A, Goel MM et al (2000) Overexpression of p53 protein in gallbladder carcinoma in North India. Eur J Surg Oncol 26:164–167

    Article  CAS  PubMed  Google Scholar 

  10. Balaram P, Alex S, Panikkar B et al (2004) Adhesion-related proteins E-cadherin, P-cadherin, CD44, and CD44v6, and antimetastatic protein nm23H1 in complete hydatidiform moles in relation to invasion potential. Int J Gynecol Cancer 14:532–539

    Article  CAS  PubMed  Google Scholar 

  11. Priya TP, Kapoor VK, Krishnani N et al (2009) Fragile histidine triad (FHIT) gene and its association with p53 protein expression in the progression of gall bladder cancer. Cancer Invest 27:764–773

    Article  CAS  PubMed  Google Scholar 

  12. Ito H, Matros E, Brooks DC et al (2004) Treatment outcomes associated with surgery for gallbladder cancer: a 20-year experience. J Gastrointest Surg 8:183–190

    Article  PubMed  Google Scholar 

  13. Zhang SH, Cong WM, Xian ZH et al (2005) Clinicopathological significance of loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in China. World J Gastroenterol 11:3034–3039

    CAS  PubMed  Google Scholar 

  14. Pecina-Slaus N, Kljaic M, Nikuseva-Martic T (2005) Loss of heterozygosity of APC and CDH1 genes in laryngeal squamous cell carcinoma. Pathol Res Pract 201:557–563

    Article  CAS  PubMed  Google Scholar 

  15. Wei Y, Van Nhieu JT, Prigent S et al (2002) Altered expression of E-cadherin in hepatocellular carcinoma: correlations with genetic alterations, beta-catenin expression, and clinical features. Hepatology 36:692–701

    Article  CAS  PubMed  Google Scholar 

  16. Moreno-Bueno G, Hardisson D, Sarrio D et al (2003) Abnormalities of E- and P-cadherin and catenin (beta-, gamma-catenin, and p120ctn) expression in endometrial cancer and endometrial atypical hyperplasia. J Pathol 199:471–478

    Article  CAS  PubMed  Google Scholar 

  17. Grady WM, Willis J, Guilford PJ et al (2000) Methylation of the promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet 26:16–17

    Article  CAS  PubMed  Google Scholar 

  18. Soares P, Berx G, van Roy F et al (1997) E-cadherin gene alterations are rare events in thyroid tumors. Int J Cancer 70:32–38

    Article  CAS  PubMed  Google Scholar 

  19. Cheng CW, Wu PE, Yu JC et al (2001) Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene. Oncogene 20:3814–3823

    Article  CAS  PubMed  Google Scholar 

  20. Bukholm IK, Nesland JM, Karesen R et al (1997) Expression of E-cadherin and its relation to the p53 protein status in human breast carcinomas. Virchows Arch 431:317–321

    Article  CAS  PubMed  Google Scholar 

  21. Stocklein H, Smardova J, Macak J et al (2008) Detailed mapping of chromosome 17p deletions reveals HIC1 as a novel tumor suppressor gene candidate telomeric to TP53 in diffuse large B-cell lymphoma. Oncogene 27:2613–2625

    Article  CAS  PubMed  Google Scholar 

  22. Karabulut Z, Besim H, Hamamci O et al (2003) Xanthogranulomatous cholecystitis. Retrospective analysis of 12 cases. Acta Chir Belg 103:297–299

    CAS  PubMed  Google Scholar 

  23. Hofseth LJ, Khan MA, Ambrose M et al (2003) The adaptive imbalance in base excision-repair enzymes generates microsatellite instability in chronic inflammation. J Clin Invest 112:1887–1894

    CAS  PubMed  Google Scholar 

  24. Yanagisawa N, Mikami T, Yamashita K et al (2003) Microsatellite instability in chronic cholecystitis is indicative of an early stage in gallbladder carcinogenesis. Am J Clin Pathol 120:413–417

    Article  CAS  PubMed  Google Scholar 

  25. Schottenfeld D, Beebe-Dimmer J (2006) Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. CA Cancer J Clin 56:69–83

    Article  PubMed  Google Scholar 

  26. Tazuma S, Kajiyama G (2001) Carcinogenesis of malignant lesions of the gallbladder. The impact of chronic inflammation and gallstones. Langenbeck’s Arch Surg 386:224–229

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was undertaken with the grant from the Department of Biotechnology (DBT), Government of India. T. Padma Priya received a fellowship from the Council of Scientific and Industrial Research (CSIR), Government of India for carrying out this study. We are thankful to Shraddha Srivastava and Sanjay Kumar Johari for the technical help. We are also grateful to all the patients for their participation in the study and informed consent was obtained from all of them.

Conflict of interest statement

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, UP, 226014, India

    T. Padma Priya & Suraksha Agrawal

  2. Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, UP, India

    V. K. Kapoor

  3. Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, UP, 226014, India

    N. Krishnani & Vinita Agrawal

Authors
  1. T. Padma Priya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. K. Kapoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. Krishnani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vinita Agrawal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Suraksha Agrawal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. Padma Priya.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Priya, T.P., Kapoor, V.K., Krishnani, N. et al. Role of E-cadherin gene in gall bladder cancer and its precursor lesions. Virchows Arch 456, 507–514 (2010). https://doi.org/10.1007/s00428-010-0908-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-010-0908-6

Keywords

Search

Navigation