Expression of epidermal growth factor receptor, p53, Bcl2, vascular endothelial growth factor, cyclooxygenase-2, cyclin D1, human epidermal receptor-2 and Ki-67: Association with clinicopathological profiles and outcomes in gallbladder carcinoma

Doval, Dinesh Chandra; Azam, Saud; Sinha, Rajesh Kumar; Batra, Ullas; Mehta, Anurag

doi:10.4103/1477-3163.139450

Cited by 23 publications

(5 citation statements)

References 38 publications

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“…We also observed significant somatic mutations in chromatin modifier genes such as SF3B1 , ATRX , CREBBP and EZH2 that have not been reported earlier in gallbladder cancer, indicating potential therapeutic options. Analyzing the potential effects of somatic alterations on survival of gallbladder cancer patients, we observed a trend among patients with wild type TP53 to survive longer than patients with TP53 mutations, which is known to predict failure of chemotherapy in several cancer types 50 and is consistent with previous reports observed in gallbladder cancer 51.…”

Section: Discussionsupporting

confidence: 90%

ERBB2 and KRAS alterations mediate response to EGFR inhibitors in early stage gallbladder cancer

Iyer

Shrikhande

Ranjan

et al. 2018

Intl Journal of Cancer

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The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. Our integrated analysis of whole exome sequencing, copy number alterations, immunohistochemical, and phospho-proteome array profiling indicates ERBB2 alterations in 40% early-stage rare gallbladder tumors, among an ethnically distinct population not studied before, that occurs through overexpression in 24% (n=25) and recurrent mutations in 14% tumors (n=44); along with co-occurring KRAS mutation in 7% tumors (n=44). We demonstrate that ERBB2 heterodimerize with EGFR to constitutively activate the ErbB signaling pathway in gallbladder cells. Consistent with this, treatment with ERBB2-specific, EGFR-specific shRNA or with a covalent EGFR family inhibitor Afatninb inhibits tumor-associated characteristics of the gallbladder cancer cells. Furthermore, we observe an in vivo reduction in tumor size of gallbladder xenografts in response to Afatinib is paralleled by a reduction in the amounts of phospho-ERK, in tumors harboring KRAS (G13D) mutation but not in KRAS (G12V) mutation, supporting an essential role of the ErbB pathway. In overall, besides implicating ERBB2 as an important therapeutic target under neo-adjuvant or adjuvant settings, we present the first evidence that the presence of KRAS mutations may preclude gallbladder cancer patients to respond to anti-EGFR treatment, similar to a clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer.

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Section: Discussionsupporting

confidence: 90%

ERBB2 and KRAS alterations mediate response to EGFR inhibitors in early stage gallbladder cancer

Iyer

Shrikhande

Ranjan

et al. 2018

Intl Journal of Cancer

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“…Like the Doval et al . study, which has shown Ki-67 expression was higher in patients of age group <40 years and patients with poorly differentiated tumor,[ 18 ] the present study has shown that Ki-67 has higher expression <40 years of age and more in females, but the results were not statically significant ( P = 0.308). Ki-67 did not provide any correlation with the biomarker expression CEA, CA-125.…”

Section: Discussioncontrasting

confidence: 64%

Expression and clinicopathological correlation of Ki-67 in gallbladder carcinoma

Gupta

Rajput

et al. 2021

J Carcinog

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INTRODUCTION: Gallbladder cancer is an aggressive cancer with short median survival from the time of diagnosis. Improved understanding of the pathological molecular mechanisms of gallbladder carcinogenesis is important to refine the diagnosis, prognosis, and also to develop novel targeted therapies for patients with advanced Gallbladder cancer (GBC) malignancy. Ki-67 is a marker of cell proliferation and its detection by immunohistochemistry is considered to be an effective method for the detection of prognosis in several tumors. In the present study, we have analyzed expression of immunohistochemical marker Ki-67 in gallbladder carcinoma and its correlation with clinicopathological and radiological parameters. MATERIALS AND METHODS: This prospective observational study was conducted from December 2017 to July 2020. The patients of newly diagnosed gallbladder cancer were enrolled as per the inclusion and exclusion criteria defined in the study protocol. Contrast-enhanced computer tomography of the chest and abdomen and serum tumor markers such as carbohydrate antigen (CA)-19.9, carcinoembryonic antigen, and CA 125 were done. Immunohistochemical expression of Ki-67 was evaluated on biopsy tissue from the gallbladder mass. RESULTS: Fifty newly diagnosed patients of carcinoma gallbladder were included in the present study. The correlation was studied between clinicodemographic parameters and Ki-67, but no association was found with age, gender, and symptoms. There was a weak positive correlation between Ki-67 and direct bilirubin, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, and alkaline phosphatase ( P = 0.094; 0.126; 0.542; and 0.328, respectively). There was a weak positive correlation between body mass index (Kg/m 2 ) and Ki-67, but this correlation was not statistically significant ( P = 0.304). CONCLUSIONS: Ki-67 is a marker of proliferation and it correlated with histological differentiation, jaundice and liver function tests, presence of stones, and location of metastases but did not correlate with stage and extent of disease.

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“…[ 20 ] and Doval et al . [ 21 ] found marked variation in result. It could be assumed due to the use of different scoring systems adopted by different authors.…”

Section: Discussionmentioning

confidence: 99%

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

Gupta¹,

Gupta²,

Mani³

et al. 2021

J Carcinog

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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.

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Expression of epidermal growth factor receptor, p53, Bcl2, vascular endothelial growth factor, cyclooxygenase-2, cyclin D1, human epidermal receptor-2 and Ki-67: Association with clinicopathological profiles and outcomes in gallbladder carcinoma

Cited by 23 publications

References 38 publications

ERBB2 and KRAS alterations mediate response to EGFR inhibitors in early stage gallbladder cancer

ERBB2 and KRAS alterations mediate response to EGFR inhibitors in early stage gallbladder cancer

Expression and clinicopathological correlation of Ki-67 in gallbladder carcinoma

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

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