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.

Background While Gallbladder carcinoma is comparatively rare, benign diseases of the gallbladder are highly prevalent and maybe either symptomatic or asymptomatic. They present themselves usually as polyps, Cholelithiasis (gallstones) and Cholecystitis (inflammation of the gallbladder) ,Gallstones are one of the most frequently reported diseases of the gallbladder. They are further associated with metaplasia, chronic inflammation and are thought to contribute to carcinogenesis .The aggressive biologic behavior of the carcinoma and non-availability of sensitive screening tests for early detection may be responsible for the poor prognosis associated with GBC.  Material and Methods All consecutive patients diagnosed with neoplastic and non-neoplastic gallbladder lesions in the Department of Pathology, Subharti Medical College were included in the study between the year 2017-2019. The hematoxylin and Eosin stained biopsies of 320 patients were assessed and out of them 100 patients were chosen as the sample for the study. The clinicopatholgical data of the 100 patients were compiled into a data base and de-identified.  Results: Related to presence of stone, there was significant difference between the Neoplastic and non-neoplastic group among male (p=0.007). There was  also significant difference between the Neoplastic and non-neoplastic in female (p=0.02). It was analyzed that there had been a significant difference between the neoplastic and non neoplastic tumour morphology and age distribution among males. The neoplastic tumours were highest in >60 years age group  while neoplastic tumours were highest among 45-60 years age group . There was significant difference between the neoplastic and non neoplastic lesions related to each of the biomarkers. The mean difference between the neoplastic and non neoplastic was highest in the p53 biomarkers followed by cyclin D. The Relationship between the different types of Biomarkers in the neoplastic lesions and there were moderate to good correlation was present between the each biomarkers.  Conclusion: The minimal response of advanced cases of GBC to traditional treatments calls for new prognostic and treatment perspectives to be identified. Novel prognostic biomarkers could bring about the needed breakthrough in this regard as they will help in the identification of patients who will benefit tremendously from adjuvant and targeted therapies.