Utility of triple tumor markers CA19-9, CA125 and CEA in predicting advanced stage of carcinoma gallbladder: a retrospective study

Navin Kumar, Deepak Rajput, Amit Gupta, Varun Popuri, Ashikesh Kundal, Jyoti Sharma, Nisanth Puliyath, Sruthi Shasheendran


Background: A combination of serum tumor markers are used in the evaluation and prognosis of carcinoma gallbladder (GBC). Aim of the study was to find the significance of combined use of CA19-9, CA125 and CEA in advanced stage of GBC and to find the cut-off value of each of these tumor markers in metastatic GBC.   

Methods: This was a retrospective observational cohort study over 1 year, which was carried out in 42 cases of advanced GBC. The patients were grouped in to locally advanced and metastatic stage on the basis of CECT scan findings. CA19-9, CA125 and CEA were assayed in all patients. These tumor markers were analysed with these two groups of GBCs. Statistical analysis was performed using R statistical software v3.6.2.

Results: Out of 42 cases CA19-9 was elevated in 18 (78%), CA125 in 16 (70%) and CEA in 9 (39%) patients with metastatic disease. The cut-off value of CA19-9, CA125 and CEA was determined by ROC curve were >109 U/ml, 55.4 U/ml and 2.56 μg/l respectively. CA19-9 had the highest sensitivity 78.3% followed by CA125 69.6% and CEA has the highest specificity 68.4% for the diagnosis of metastatic stage of the disease. Specificity of these tumor markers were highest when used in combination.

Conclusions: Combined use of triple tumor markers increases its specificity in the diagnosis of advanced stage of GBC but their cut-off level is statistically not significant in predicting metastatic GBC.


Tumor markers in carcinoma gallbladder, Cut-off value of CA19-9, CA125 and CEA in metastatic carcinoma gallbladder, Specific tumor markers in gallbladder cancer

Full Text:



Hundal R, Shaffer EA. Gallbladder cancer: epidemiology and outcome. Clin Epidemiol. 2014;6:99-109.

Wistuba II, Gazdar AF. Gallbladder cancer: lessons from a rare tumour. Nat Rev Cancer. 2004;4:695-706.

Chaube A, Tewari M, Singh U, Shukla HS. CA 125: a potential tumor marker for gallbladder cancer. J Surg Oncol. 2006;93(8):665‐9.

Donnel MAC, Kirk VEA, Austin KJ. Expression of CA 125 by progetational bovine endometrium: Prospective regulation and function. Reproduction. 2003;126:615-20.

Nouwen EJ, Pollet DE, Eerdeckens MW. Immunohistochemical localization of placental alkaline phosphatase, carcinoembryonic antigen and cancer antigen 125 in normal and neoplastic human lung. Cancer Res. 1986;46:866-76.

Canney P, Moore M, Wilkinson P. Ovarian cancer antigen CA125; a prospective clinical assessment of the role as a tumour marker. Br J Cancer. 1984;50:765-9.

Speers CW, Hayes DF. Tumor Biomarkers. In: De Vita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology. 11th ed. LWW Wolters Kluwer; 2018:974-975.

Zhang Y, Yang J, Li H, Wu Y, Zhang H, Chen W, et al. Tumor markers CA19-9, CA242 and CEA in the diagnosis of pancreatic cancer: a meta-analysis. Int J Clin Exp Med. 2015;8:11683-91.

Reitz D, Gerger A, Seidel J, Kornprat P, Samonigg H, Stotz M, et al. Combination of tumour markers CEA and CA19-9 improves the prognostic prediction in patients with pancreatic cancer. J Clin Pathol. 2015;68:427-33.

Goonetilleke KS, Siriwardena AK. Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol. 2007;33:266-70.

Hatzaras I, Schmidt C, Muscarella P, Melvin WS, Ellison EC, Bloomston M, et al. Elevated CA 19-9 portends poor prognosis in patients undergoing resection of biliary malignancies. HPB. 2010;12:134-8.

Wang YF, Feng FL, Zhao XH. Combined detection tumor markers for diagnosis and prognosis of gallbladder cancer. World J Gastroenterol. 2014;20(14):4085‐92.

Grunnet M, Sorensen MM. Serum tumor markers in bile duct cancer: a review. Biomarkers. 2014;19:437-43.

Shukla VK, Gurubachan, Sharma D, Dixit VK, Usha. Diagnostic value of serum CA242, CA 19-9, CA 15-3 and CA 125 in patients with carcinoma of the gallbladder. Trop Gastroenterol. 2006;27(4):160‐5.