Prognostic Significance of HER-2 and p53 Expression in Gallbladder Carcinoma in North Indian Patients

Singh, Anjali; Mishra, Pramod Kumar; Saluja, Sundeep Singh; Talikoti, Majid Ahmed; Kirtani, Pawan; Najmi, Abul Kalam

doi:10.1159/000450999

Cited by 13 publications

(6 citation statements)

References 24 publications

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“…In addition to the well-known pathological prognostic factors, many molecular features associated with GBC pathogenesis have been proposed as potential biomarkers that might help stratify patients with GBC. Thus, overexpression of p53 [89][90][91], mutations in KRAS [92], amplification of HER2/neu [91,93], overexpression of EGFR [94,95], among other potential molecular prognostic factors such as microRNAs (recently reviewed by Montalvo-Jave et al [5]) have been associated with worse prognosis. Most potential markers have been evaluated in formalin-fixed paraffin-embedded (FFPE) cancer biopsy sections by immunohistochemical analysis, but there are also promising candidates based on RNA/DNA and serum protein detection.…”

Section: Molecular Prognostic Biomarkersmentioning

confidence: 99%

Current and New Biomarkers for Early Detection, Prognostic Stratification, and Management of Gallbladder Cancer Patients

García

Lamarca

Díaz

et al. 2020

Cancers

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Gallbladder cancer (GBC) is an aggressive disease that shows evident geographic variation and is characterized by a poor prognosis, mainly due to the late diagnosis and ineffective treatment. Genetic variants associated with GBC susceptibility, including polymorphisms within the toll-like receptors TLR2 and TLR4, the cytochrome P450 1A1 (CYP1A1), and the ATP-binding cassette (ABC) transporter ABCG8 genes, represent promising biomarkers for the stratification of patients at higher risk of GBC; thus, showing potential to prioritize cholecystectomy, particularly considering that early diagnosis is difficult due to the absence of specific signs and symptoms. Similarly, our better understanding of the gallbladder carcinogenic processes has led to identify several cellular and molecular events that may influence patient management, including HER2 aberrations, high tumor mutational burden, microsatellite instability, among others. Despite these reports on interesting and promising markers for risk assessment, diagnosis, and prognosis; there is an unmet need for reliable and validated biomarkers that can improve the management of GBC patients and support clinical decision-making. This review article examines the most potentially significant biomarkers of susceptibility, diagnosis, prognosis, and therapy selection for GBC patients, highlighting the need to find and validate existing and new molecular biomarkers to improve patient outcomes.

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Section: Molecular Prognostic Biomarkersmentioning

confidence: 99%

Current and New Biomarkers for Early Detection, Prognostic Stratification, and Management of Gallbladder Cancer Patients

García

Lamarca

Díaz

et al. 2020

Cancers

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“…Aberrant HER family signaling may be important in the development and progression of GBC 15,20 . Some studies reported adverse prognostic impact of HER2 expression 16,[23][24][25][26]43 , but others, including ours, did not show such correlation 27,44 . A few studies have investigated anti-HER2 therapy in advanced GBC [45][46][47][48][49] .…”

Section: Discussionmentioning

confidence: 52%

Expression of Female Sex Hormone Receptors, Connective Tissue Growth Factor and HER2 in Gallbladder Cancer

Hryciuk

Pęksa

Bieńkowski

et al. 2020

Sci Rep

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Gallbladder cancer (GBc) is a highly malignant tumor with poorly understood etiology. An insight into phenotypic features of this malignancy may add to the knowledge of its carcinogenesis and pave the way to new therapeutic approaches. We assessed the expression of female sex hormone receptors (eRα, eRβ, PR), connective tissue growth factor (CTGF) and HER2 in GBC, and adjacent normal tissue (nt), and determined their prognostic impact. immunohistochemical (iHc) expression of all biomarkers was performed in formalin-fixed, paraffin-embedded specimens in 60 Caucasian GBC patients (51 women and 9 men). ERβ, cytoPR and CTGF expression were found in 89%, 27%, 91% of GBC, and in 63%, 87%, 100% of NT, respectively. No ERα expression was found in GBC and NT. Strong (3+) HER2 expression by iHc or HER2 amplification was seen in five GBC (10.4%). A positive correlation was found between HER2 and CTGF and ERβ expression in GBc and matched nt. in the multivariate analysis, patient age >70 years, tumor size and ERβ expression in GBc was highly predictive for oS (p = 0.003). The correlation between HER2, CTGF and ERβ expression in GBc and nt may indicate the interaction of these pathways in physiological processes and gallbladder pathology. Gallbladder cancer (GBC) is an aggressive malignant tumor originating from epithelial cells of the mucous membrane. The etiology of GBC is poorly understood, and its global prevalence is characterized by considerable regional variations 1-4. The highest incidence is reported in Chile, India, Pakistan, Bolivia, Central Europe, Israel, and in Native Americans and Americans of Mexican origin 1-4. The risk of developing GBC is higher in patients with chronic inflammatory processes caused by gallstones with resulting calcification of the gallbladder wall ("porcelain gallbladder"), and with infections such as Salmonella typhi or Salmonella paratyphi 3-5. GBC is about two to six times more common in women compared to men, and its incidence steadily increases with age 1-5. Estrogens are key signaling molecules that regulate various physiological processes and play a major role in many pathological conditions, such as hormone-dependent cancers. Expression of female sex hormone receptors in GBC has been analyzed in a few studies including mainly Asian populations, and provided inconsistent results 6-14. Several small studies demonstrated overexpression of human epidermal growth factor receptor type 2 (HER2) and HER gene amplifications or mutations 15-27. Connective Tissue Growth Factor (CTGF) was found to be expressed in various stages of the GBC carcinogenesis 28. GBC carries a poor prognosis and most patients succumb to their disease. An insight into phenotypic features of this tumor may add to the knowledge of its carcinogenesis and pave the way to new therapeutic approaches. In the present study we investigated the expression of female sex hormone receptors: estrogen receptor alpha (ERα), ER beta (ERβ) and progesterone (PR), as well as CTGF and HER2 in a relatively large group of Caucasian GBC pat...

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“…Singh et al also found similar results in their study on gall bladder carcinoma. 13 Ashai et al studied the HER2/neu expression in correlation to advanced tumour stage of gall bladder carcinoma and showed that 46% cases were score 1+, 23% were score 2+, 9% cases were 3+ and 19% cases were negative. 14 We also evaluated HER-2/neu expression in gall bladder carcinoma and found similar results.…”

Section: Discussionmentioning

confidence: 99%

A histopathological evaluation of gall bladder cancer with special reference to HER2/neu and E-cadherin in Southern part of Assam

Choudhury

Deka

et al. 2021

Int J Res Med Sci

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Background/Objective: Gall bladder carcinoma (GBC) is an aggressive malignancy with high mortality and aggressive course, with palliation as the only available option. The signs and symptoms of gall bladder arcinoma are not specific and often present late. Diagnosis is, therefore, often made at advanced stage with poorer outcomes. Identifying biomarkers and cancer specific cellular targets, that will pave the way for novel therapeutic approaches and early diagnosis for gall bladder carcinoma, is urgently needed. Proto-oncogenes (HER-2) and E-Cadherin are commonly deregulated in gallbladder cancer (GBC). This study evaluates the prognostic significance of HER-2 and E-Cadherin in GBC patients in Silchar Medical College.Our main objective was to evaluate frequency of HER-2/neu overexpression in GBC and to seek its correlation, if any with conventional clinicopathological parameters and survival.Methods: A total of 168 cases were received and evaluated for Gall Bladder cancer and control specimens were prospectively collected from 2018-2020. Immunohistochemical staining was done using monoclonal antibodies to semiquantitatively evaluate HER-2 and E-Cadherin protein expression. The criterion for HER-2 and E-Cadherin positivity was set at 10% and >5% tumor cells showing complete, membranous staining. Clinicopathological correlations were drawn with major clinical outcomes. Results: It was observed that out of 168 cases the male to female ratio is 1:5 with highest number of cases in the age group of 50-59 , i.e., 70 cases with 41.7%. The most common location in this study was fundus with 69% of cases (116 out 0f 168), most commonly presented as biliary colic with 56 number of cases. Grading was also done in 168 cases where most number of cases were moderately differentiated with 86 number of cases with a percentage of 51%. Expression of Her2Neu and E-Cadherin was evaluated where highest number of cases were seen with 1+ score in the IHC expressions of both the markers with 81 and 61 number of cases respectively. Conclusion: The increasing global incidence, late presentation leading to poor prognosis and lack of effective therapy make the management of gall bladderv carcinoma really challenging. Our study shows the abnormal expression of HER-2 and E-Cadherin expression in gall bladder carcinoma patients in Southern Assam and suggests that these two markers can be used for potential tool for early detection of gall bladder carcinoma and also can be used for targeted therapy in gall bladder carcinoma.

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Prognostic Significance of HER-2 and p53 Expression in Gallbladder Carcinoma in North Indian Patients

Cited by 13 publications

References 24 publications

Current and New Biomarkers for Early Detection, Prognostic Stratification, and Management of Gallbladder Cancer Patients

Current and New Biomarkers for Early Detection, Prognostic Stratification, and Management of Gallbladder Cancer Patients

Expression of Female Sex Hormone Receptors, Connective Tissue Growth Factor and HER2 in Gallbladder Cancer

A histopathological evaluation of gall bladder cancer with special reference to HER2/neu and E-cadherin in Southern part of Assam

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