Background: Gallbladder carcinoma is the most common malignancy in the biliary tract, the fifth commonest cancer of the gastrointestinal tract. Oncogenes (beta-catenin) has been shown to be involved in the development and progression of gallbladder carcinoma. The present study has been conducted with an aim to study the expression patterns of beta-catenin in different gallbladder tissues to elucidate the role of this oncogene in carcinogenesis and to evaluate its relationship with tumor progression.

Materials and Methods:  The study was conducted on histological sections from surgically resected 112 specimens of gallbladder tissue lesions operated at the Department of Surgery, Nehru Chikitsalaya, Gorakhpur which included 66 cases of chronic cholecystitis, 34 cases of gallbladder carcinoma and 12 specimens of gallbladder controls as part of other surgical procedures with no pathology in the gall bladder.

Results: Beta-catenin nuclear expression in gallbladder cancer was significantly higher than in chronic cholecystitis and normal gallbladders (P < 0.0001). With increasing (T) depth of tumor invasion (P = 0.0231) and stage of the lesions (p= 0.0226), there is also an increase in the nuclear expression of beta-catenin. The level of beta-catenin expression increased from 44.44% in well differentiated (low grade) to 100% in poorly differentiated (high grade) tumor (P = 0.0463).Thus suggesting a role in tumor progression.

Conclusion: In present study, it was observed that expression of beta‑catenin get altered in gallbladder carcinoma and has a significant role in carcinogenesis and progression of gallbladder carcinoma.

Keywords: Gallbladder carcinoma, Beta-catenin, “T”- depth of tumor invasion, stage of the lesion.

1. Park JS, Yoon DS, Kim KS, et al: Analysis of prognostic factors after curative resection for gallbladder carcinoma. Korean J Gastroenterol, 2006; 48: 32‑36.
2. Ghosh M, Sakhuja P, Singh S, Agarwal AK. p53 and beta-catenin expression in gallbladder tissues and correlation with tumor progression in gallbladder cancer. Saudi J Gastroenterol 2013;19:34-9.
3. Chang H, Jee C, Kim W. Mutation and altered expression of beta‑catenin during gallbladder carcinogenesis. Am J Surg Pathol 2002;26:758‑
4. Puhalla H, Herberger B, Soleiman A, Filipits M, Laengle F, Gruenberger T, et al. E‑cadherin and beta‑catenin expression in normal, inflamed and cancerous gallbladder tissue. Anticancer Res 2005;25:4249‑54
5. Fleming ID, Cooper JS, Henson DE, Hutter RV, Kennedy BJ, Murphy GP, et al. AJCC cancer staging manual. 5th ed. Philadelphia, New York: Lippincot‑Raven; 1997.
6. Albores‑Saavedra J, Henson D, Klimstra D. Tumours of the gallbladder, extrahepatic bile ducts and ampulla of vater. Washington, DC: Armed Forces Institute of Pathology; 2000. p. 668.
7. Manuela Stancu et al. Romanian Journal of Morphology and Embryology 2007, 48(4):335–342.
8. Rakesh B , Rajendra G. A prospective clinicopathological study of 50 cases of chronic calculous cholecystitis in the local population: 2013;12;35:6706-6716.
9. Thamil Selvi, Pammy Sinha, P.M. Subramaniam, P.G. Konapur, C.V. Prabha. A clinicopathological study of cholecystitis with special reference to analysis of cholelithiasis. International Journal of Basic Medical Science-July 2011, Vol:2, Issue :2.
10. S K umar , Tiwari A . Evaluation of Microsatellite Instability and Apoptosis in Gall Bladder Malignancy from Patients of a Cohort Exposed to Methylisocyanate. J Carcinog Mutagen 2014:5:171.
11. Rizwan Ahmad Khan, Mohammad Amanullah Khan Advanced presentation of Gallbladder cancer: Epidemioclinico-pathological study to evaluate the risk factors and assess the outcome 2010;60:217; 2010.
12. Ramesh S Waghmare, Rima N Kamat. Incidental Gall Bladder Carcinoma in Patients Undergoing Cholecystectomy : A Report of 7 Cases, 2014; 62
13. Gupta SC , Mishra V., Singh PA et al. Gall stone and carcinoma gallbladder. Indian J Pathol Micribiol 2000;43:147-154.
14. Adam R,Stranahan A. Cholecystitis and cholelithiasis; an analytical report of 1,104 operative cases. Surg Gynecol Obstet 1947; 85:776-84.
15. Glenn F, Frey C. Re-evaluation of the treatment of pancreatitis associated with biliary tract diseases. Ann Surg 1964; 160: 723-36.6
16. Khanna R, Chansuria R, Kumar M, Shukla HS. Histological changes in gallbladder due to stone disease. Indian J Surg 2006; 68:201-4.
17. Aulakh R, Mohan H, Attri AK, et al. Comparative study of serum lipid profile and gallstone disease. Indian J Pathol Microbiol 2007; 50:308-12. 29.
18. Sayeed Unisa, Palepu Jagannath, Vinay Dhir, Chiranjeeva Khandelwal, Lalatendu Sarangi, and Tarun Kumar Roy. Population – based study to estimate prevalence and determine risk factors of gallbladder diseases in the rural Gangetic basin of North Indian HPB (Oxford). 2011 February; 13(20):117-125.
19. Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer 2006; 118:1591.
20. Santanu Acharyya, Amitabha Chakrobarti, Sourav Sau, Partha Dasgupta, Sandip Ghosh, Anjali Majumdar Incidental Finding of Gall Bladder Carcinoma : A Retrospective Study.2012;116-120
21. Tran H Giang, Tran TB Ngoc and Lewis A Hassell. Carcinoma involving the gallbladder: a retrospective review of 23 cases - pitfalls in diagnosis of gallbladder carcinoma .Diagnostic Pathology 2012; 7:10.
22. Tyagi SP, Tyagi N, Maheshwari V, Ashraf SM, Sahoo P. Morphological changes in diseased gallbladder: a study of 415 cholecystectomies at Aligarh. (J Indian Med Assoc.1992 Jul;90(7):178-81.
23. Dr Arathi. NA, Seema Awasthi A, Ashutosh Kumar A .Pathological Profile Of Cholecystectomies At A Tertiary Centre 2013:2:1;28-38 .
24. Rohin Mittal, Mark Ranjan, Jesudason, Sukria Nayak. Selective histopathology in cholecystectomy for gallbladder disease. Indian J Gastroentrol 2010 , 29 (1):32-36.
25. Zahrani IH, Mansoor I. Gallbladder pathologies and cholelithiasis. Saudi Med J. 2001 Oct;22(10):885-9.
26. Moema Gonçalves Pinheiro Veloso, Daniel Nava Rodrigues. Gallbladder carcinoma: clinicopathological study of 24 cases , 2011;vol.47 no.4 Rio de Janeiro .
27. Kimura Y, Furuhata T, Mukaiya M, Kihara C, Kawakami M, Okita K, et al. Frequent beta‑catenin alteration in gallbladder carcinomas. J Exp Clin Cancer Res 2003;22:321‑
28. Puhalla H, Herberger B, Soleiman A, Filipits M, Laengle F, Gruenberger T, et al. E‑cadherin and beta‑catenin expression in normal, inflamed and cancerous gallbladder tissue. Anticancer Res 2005;25:4249‑
29. Moon W, Park H, Lee H, Pai R, Tarnawski A, Kim K, et al. Co‑expression of Cox‑2, C‑Met and beta‑catenin in cells forming invasive front of gallbladder cancer. Cancer Res 2005;37:171‑6.

Dr Chandrawati

B.R.D.M.C. Gorakhpur