Expression of Human epidermal growth factor receptor 2, Survivin, Enhancer of zeste homolog -2, Cyclooxygenase-2, p53 and p16 molecular markers in Gall bladder carcinoma

Abstract

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 (χ 2 = 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 (χ 2 = 7.017, P = 0.037 and χ 2 = 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.

Clinicopathological And Prognostic Significance Of Immuno-Expression Of Cyclin D1, E-Cadherin, EGFR, HER- 2, Ki67, And P53 In Gall Bladder Cancer And Its Precursor Lesions-A Review

“…HER2 is another transmembrane tyrosine kinase receptor protein whose overexpression has been detected and correlated to the progression of several human cancers [63,64]. Overexpression of HER2 in GBC has been demonstrated in several studies [64,65,66] but the frequency of overexpression and gene amplification has been found to be lower than other markers. HER2 protein overexpression in relation to gene amplification is yet to be established in GBC [65].…”

“…HER2 levels reported across different studies conducted on GBC samples exhibit a large variation. These reported variations in HER2 expression have been attributed to the choice of different assays and scoring systems with varying specificity and sensitivity towards GBC [66]. The most commonly used scoring systems in these studies are based on the criteria used for gastric cancer [68] and breast cancer [66] along with the Hercep test scoring system [54].…”

“…These reported variations in HER2 expression have been attributed to the choice of different assays and scoring systems with varying specificity and sensitivity towards GBC [66]. The most commonly used scoring systems in these studies are based on the criteria used for gastric cancer [68] and breast cancer [66] along with the Hercep test scoring system [54]. Though, Toledo et al argued that HER2 immunoreactivity observed in basolateral cell membrane domain of metaplastic gallbladder epithelium in GBC could not be compared to that scored by Hercep Test as it is based on the immunoreactivity observed in invasive breast cancer cells that are neoplastic non-polarized cells, Kawamato et al suggested that Hercep test could be used as an acceptable predictor to determine FISH positivity of HER2 gene amplification [54].…”

Recent advances in biosensor devices for HER-2 cancer biomarker detection

“…4 The epidermal growth factor receptor family includes HER1 (EGFR), HER-2 (erbB2), HER3 (erbB3), and HER4 (erbB4). 5,6 These RTKs are transmembrane single subunit glycoproteins with intracellular tyrosine kinase, a catalytic domain, an extracellular ligand-binding domain, and a transmembrane domain. HER-2, also known as receptor tyrosine-protein kinase erbB-2, is a member of the EGFR family of receptor tyrosine kinases.…”

Diagnostic and Prognostic Impact of Progesterone Receptor Immunohistochemistry: A Study Evaluating More Than 16,000 Tumors

“…Data on PR immunostaining in the literature typically lacks associations with patient age, gender, or stage in cancer [6][7][8][9][10][11][12][13][14] and is overall highly variable. For example, the reported range of PR positivity ranges from 0 to 76% in colorectal cancer [6][7][8], from 0 to 52% in adenocarcinoma of the gall bladder [9,10,15,16], from 0 to 85% in prostate cancer [11,17,18], from 0 to 63% in non-small-cell lung cancer [12,19,20], from 38.7 to 75.8% in papillary thyroid carcinoma [13,14,[21][22][23][24], and from 15.2 to 100% in angiomyolipoma of the kidney [25][26][27]. These conflicting data are likely to be caused by the use of different antibodies, staining protocols, and interpretation criteria in these studies.…”