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

Abstract

Gallbladder carcinoma (GBC) is an aggressive and common cancer of the biliary tract. It develops on the epithelia of the gallbladder and is has the ability to rapidly metastasize to nearby organs and distant lymph nodes. It also has the shortest median survival time when compared to other biliary tract cancers [1]. As the disease rarely presents a distinct set of clinical symptoms, delayed diagnosis contributes heavily towards the negative prognosis widely associated with the disease [2]. The molecular mechanisms and underlying changes that bring about carcinogenesis of the gallbladder epithelia, though widely studied have not been fully understood. Chronic inflammation [3], dysplasia [4] and adenoma [5] among other factors have been observed to increase the risk of developing GBC among other risk factors. With current treatment options offering only limited curative capacities, identifying and studying biomarkers with potential to speed up prognostics and having clinical applicability has become a priority. These biomarkers, apart from playing an important role in carcinogenesis, need to be specific for GBC and their levels should vary significantly enough to differentiate between malignant and benign conditions. Though several such molecules have been identified and used in diagnostic trials, the availability of disease-specific and highly sensitive markers for GBC is yet a task to be achieved. Isolation of such prognostic markers will help in understanding disease progression [6]. Further, expression levels of these prognostic markers can be used to aid in the determination of the clinical course of action, patient response to therapy and the need for adjuvant therapy [7]. An ideal prognostic marker should be easily quantifiable with high sensitivity, specificity and its levels should significantly vary to be able to differentiate benign conditions from malignancy. A clinically applicable prognostic marker should be able to predict recurrence, survivability and need for adjuvant therapies. Several categories of markers have been studied to date and include tumour markers such as CA125, CA19-9, CEA, inflammatory markers like CRP, tumour suppressors like p53, E-cadherin etc. In this review we hope to explore the future prospects of some of these markers based on available literature.