• Fluorescence in situ hybridization
• Gallbladder carcinoma
• Human epidermal growth factor receptor-2
• Immunohistochemistry
• Overall survival
• Target therapy

• No.3/2/2/14/2018/Online Onco Fship/NCD-III Indian Council of Medical Research

• Cholecystectomy
• Extended cholecystectomy
• Gall bladder
• Gall bladder cancer
• Gall stones
• Incidental gall bladder cancer
• Radical cholecystectomy

• cancer
• cytological techniques
• gallbladder neoplasms
• immunohistochemistry
• pathology, molecular

• Female
• Humans
• Male
• Biomarkers, Tumor/metabolism
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/analysis
• Biopsy, Fine-Needle
• Case-Control Studies
• Gallbladder Neoplasms/pathology
• Gallbladder Neoplasms/genetics
• Gallbladder Neoplasms/metabolism
• Immunohistochemistry
• In Situ Hybridization, Fluorescence
• Prospective Studies
• Receptor, ErbB-2/metabolism
• Receptor, ErbB-2/genetics
• Receptor, ErbB-2/analysis

• Clinical research
• Gallbladder cancer
• India
• Surgery
• Therapeutics
• basic research

• Estrogen receptor
• gallbladder cancer
• progesterone receptor Her2/neu
• tumor marker

• Humans
• Female
• Biomarkers, Tumor
• Receptor, ErbB-2/genetics
• Receptor, ErbB-2/metabolism
• Receptors, Estrogen/metabolism
• Gallbladder Neoplasms/genetics
• Receptors, Progesterone/metabolism
• Breast Neoplasms

• Gallbladder cancer
• HER2
• HER2-Positivity criteria
• Prognosis
• Stage

Gallbladder carcinoma (GBC) is responsible for 80%–95% of biliary tract malignancies and has a dismal prognosis. Human epidermal growth factor receptor 2 (HER2) is a promising therapeutic target of GBC. Through immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods, HER2 expression and gene amplification were identified on high-output tissue microarrays (TMAs) developed in 306 GBC cases to investigate its relationship with GBC and clinicopathological characteristics. Adenocarcinomas accounted for 223 (72.9%) of the cases, with 62 (27.8%) being papillary adenocarcinoma or having partial papillary structure. HER2 positivity was studied in 16.1% (36/223) of patients with adenocarcinoma and 41.9% (26/62) in adenocarcinoma with papillary structures. For 143 radically resected primary GBC cases with 24 HER2-positive tumors, survival data were valid; the median survival time was not reached, and the 5-year survival rate was 52.9%. All patients in stages 0–I survived, and the results of the HER2-positive group and the stage II HER2-negative group were similar (p = 0.354). However, in stage III, the mortality rate in the HER2-positive group was reduced (p = 0.005) and that in stage IV was higher (p = 0.005). In conclusion, HER2 positivity was significantly higher in patients with papillary GBC. The predictive value of HER2 varies by clinical stage, with no prediction in the early stages, better in stage III, and worse in stage IV.

• Cancer biomarkers
• HER2/neu
• KRAS
• VEGF-A
• gall bladder carcinoma

• Adult
• Aged
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Carcinoma/genetics
• Carcinoma/physiopathology
• Female
• Gallbladder Neoplasms/genetics
• Gallbladder Neoplasms/physiopathology
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• India
• Lymphatic Metastasis/genetics
• Lymphatic Metastasis/physiopathology
• Male
• Middle Aged
• Pilot Projects
• Prospective Studies
• Young Adult

Gallbladder cancer (GBC) has a poor prognosis. Although complete surgical resection is the only successful approach for improving survival, additional therapeutic modalities are required for recurrent or surgically unresectable GBCs.

To determine the expression status of HER2 and the mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, immunohistochemical staining of MMR proteins and HER2 was carried out in 216 surgically resected GBCs. HER2 labeling was scored by adopting a scoring system for gastric carcinomas. Tissues scoring 0 to 2+ were defined as HER2 negative, whereas those scoring 3+ were regarded as HER2-positive. In addition, silver in situ hybridization and microsatellite instability (MSI) analysis were conducted to confirm HER2 amplification and MSI, respectively.

Three of 216 GBCs (1.3%) showed MMR protein deficiency. All three observed MSI cases exhibited dual loss of MSH2 and MSH6 protein expression. However, no cases showed loss of either MLH1 or PMS2 expression. No association was observed between MMR protein deficiency and other clinicopathological factors. HER2 amplification was noted in 30 (13.9%) GBCs and associated with Crohn-like lymphoid reaction (P = 0.023). No survival difference was observed based on HER2 overexpression or HER2 amplification status.

MMR protein deficiency and HER2 overexpression were observed in a small subset (1.3% and 13.9%, respectively) of GBCs without simultaneous occurrence of deficient MMR protein expression and HER2 overexpression. The presence of Crohn-like lymphoid reaction may help identify cases with HER2 amplification, by using hematoxylin-stained slides. Although the proportion of MMR protein-deficient- and HER2-overexpressing GBCs was small, applying immunotherapy to MMR protein-deficient GBCs and herceptin to HER2-overexpressing GBCs may provide alternative treatment options for patients with GBC.

• HER2
• cancer
• gallbladder
• microsatellite Instability
• mismatch repair proteins

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.

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.

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.

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.

• Gall bladder cancer
• expression
• immunohistochemistry
• molecular markers

• Fluorescent in situ hybridization
• HER-2/neu
• gall bladder adenocarcinoma
• immunohistochemistry

• Adenocarcinoma/genetics
• Adult
• Cholecystitis/genetics
• Female
• Gallbladder Neoplasms/genetics
• Humans
• Immunohistochemistry
• In Situ Hybridization, Fluorescence
• Male
• Middle Aged
• Receptor, ErbB-2/genetics

• Biliary tract cancer
• Gallbladder cancer
• HER2/neu
• Predictive biomarkers
• Targeted therapy

• Biliary tract cancer
• Cholangiocarcinoma
• HER2 pathway
• HER3 pathway
• Meta-analysis
• Systematic review

Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine PubMed (http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines (http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.

• Gallbladder cancer
• Epidemiology
• Molecular genetics
• Pathogenesis

• Biomarkers, Tumor/genetics
• DNA Methylation
• Epigenesis, Genetic
• Gallbladder Neoplasms/epidemiology
• Gallbladder Neoplasms/genetics
• Gallbladder Neoplasms/pathology
• Gene Expression Regulation, Neoplastic
• Genetic Predisposition to Disease
• Humans
• Loss of Heterozygosity
• Microsatellite Instability
• Molecular Epidemiology
• Mutation
• Phenotype
• Risk Factors

The inhibition of the neovascularization in tumors is a potential therapeutic target of cancer. Vascular endothelial growth inhibitor (VEGI) is a member of the TNF superfamily which has the ability to suppress the formation of new vessels in tumors. In order to study the association between VEGI gene polymorphisms and breast cancer risk, a case-control study was conducted in Chinese Han women in Northeast China.

Our study involved 708 female breast cancer patients and 685 healthy volunteers. Four SNPs of VEGI gene were analyzed through the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between VEGI gene polymorphisms and breast cancer risk was analyzed in our study. The relation between VEGI gene variants and clinical features of breast cancer including lymph node (LN) metastasis, estrogen receptor (ER), progestrogen receptor (PR), tumor protein 53 (p53), human epidermal growth factor receptor 2 (Her-2) and triple negative (ER-/PR-/Her-2-) status was analyzed as well.

We found that the CT genotype and T allele of rs6478106 were more frequent in patients than in controls. There was also a statistical difference in the distribution of C_rs6478106G_rs4263839 haplotype between patients and controls. In addition, SNP rs6478106 and rs4979462 were related with the Her-2 status.

Our results suggest that VEGI gene variants may be related to the breast cancer risk and the clinical features of breast cancer in Chinese Han women in Northeast China.

• Vascular endothelial growth inhibitor (VEGI)
• breast cancer
• single nucleotide polymorphisms (SNPs)

• Fluorescence in situ hybridization
• Gallbladder cancer
• HER2
• Heterogeneity
• Immunohistochemistry

Gallbladder cancer (GBC) is an uncommon disease in the majority of the world despite being the most common and aggressive malignancy of the biliary tree. Early diagnosis is essential for improved prognosis; however, indolent and nonspecific clinical presentations with a paucity of pathognomonic/predictive radiological features often preclude accurate identification of GBC at an early stage. As such, GBC remains a highly lethal disease, with only 10% of all patients presenting at a stage amenable to surgical resection. Among this select population, continued improvements in survival during the 21st century are attributable to aggressive radical surgery with improved surgical techniques. This paper reviews the current available literature of the 21st century on PubMed and Medline to provide a detailed summary of the epidemiology and risk factors, pathogenesis, clinical presentation, radiology, pathology, management, and prognosis of GBC.

• bile acid
• biliary tract cancer
• erbB2