Amit Gupta1, Sweety Gupta2, Rishit Mani1, Prashant Durgapal3, Bela Goyal4, Deepak Rajput1, Shalinee Rao3, Puneet Dhar5, Manoj Gupta2, Sanjeev Kishore3, Ravi Kant1
1 Department of Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
2 Department of Radiation Oncology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
3 Department of Pathology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
4 Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
5 Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
INTRODUCTION: Gallbladder cancer exhibits striking variability in the global rates, reaching epidemic levels for some regions and ethnicities. The basis of its variability resides in differences in environmental exposure and intrinsic genetic predisposition to carcinogenesis. There is little information present regarding genetic and molecular alterations in gall bladder cancer (GBC). We, therefore, have evaluated the molecular marker expression in GBC and studied their correlation with clinicopathological staging.
MATERIALS AND METHODS: This prospective observational study was conducted on newly diagnosed GBC patients from July 2017 to July 2020. After complete staging workup, the GBC biopsy samples paraffin block was tested for molecular markers estrogen receptor (ER), progesterone receptor (PR), p53, p16, Human epidermal growth factor receptor 2 (HER 2-neu), Survivin, Enhancer of zeste homolog-2 (EZH2), and Cyclooxygenase-2 (COX-2) expression by immunohistochemistry.
RESULTS: Fifty newly diagnosed patients of carcinoma gall bladder were included in the present study. Age was ranged from 29 – 69 years (mean 53.42). p53 was the most common positive marker in 74% of patients, survivin in 58%, COX-2 in 44%, and p16 in 42% whereas Her 2 neu and EZH-2 were positive in 16% of patients each. None of the patients of GBC were ER or PR positive. There was a significant difference between the various groups in terms of the distribution of histological grade and Her 2 neu (χ2 = 9.886, P = 0.014) but not with other markers. Furthermore, there was a significant difference in terms of distribution of p16 and p53 with stage (χ2 = 7.017, P = 0.037 and χ2 = 5.861, P = 0.033) respectively.
CONCLUSIONS: The present study shows the expression of molecular markers Her2 neu, p53, p16, survivin, COX-2, and EZH-2 in GBC. Now the time has come, and it is also the need of the day to establish early biomarkers of this highly lethal malignancy. It can be used in future for the detection of disease in the early phase and targeted therapy.
Keywords: Gall bladder cancer, molecular markers, expression, immunohistochemistry