scholarly journals EGFR and HER2neu Expression in Gall Bladder Carcinoma and Its Association with Clinicopathological Parameters - An Institutional Experience from North India

2021 ◽  
Vol 6 (1) ◽  
pp. 57-65
Author(s):  
Inara Abeer ◽  
Sabina Khan ◽  
Mohd. Jaseem Hasan ◽  
Musharraf Hussain

Objective: Gallbladder cancer (GBC) is the most common biliary tract malignancy found worldwide with very high incidence in North India especially Delhi region. It is characterized by poor prognosis and ineffective treatment especially in advanced stage. The aim of this study was to evaluate EGFR and HER2/neu immunoexpression in cancer patients and to correlate it with the clinicopathological parameters so as to identify GBC patients who can benefit from targeted therapy.Methods: Present study was conducted in the Department of Pathology, Hamdard Institute of Medical Sciences & Research, New Delhi. A total of 40 cases of Gallbladder carcinoma (GBC) were evaluated for Immunohistochemical expression of EGFR and HER2/neu. Clinicopathological parameters of GBC were studied and correlated with immunoexpression of EGFR and HER2 /neu. Result: The mean age of the GBC patients was 55.9 years with 90% being females. On histopathology, 34(85%) cases were conventional adenocarcinoma. The EGFR expression was positive in 29/40 cases (72.5%). It was significantly more positive in poorly differentiated grade and advanced stages of gall bladder carcinoma (P<0.05). The expression of HER2/neu was positive in 13/40 cases (32.5%). It was significantly more positive in well differentiated gall bladder carcinoma (P<0.05). Immunoexpression of EGFR was inversely related with HER2/neu expression and this association was statistically significant.Conclusion: Among GBC patients, EGFR expression and HER2/neu expression was 72.5% and 32.5%, respectively. Significant EGFR expression was seen in poorly differentiated and advanced stage cancers while significant HER2/neu expression was seen in well differentiated gall bladder carcinomas. To conclude, these two markers HER2/neu and EGFR can be used as predictive and prognostic markers respectively, with rationale to further explore the use of anti-HER2 and anti- EGFR therapy in gall bladder cancer.

Author(s):  
Chhanda Das ◽  
Madhumita Mukhopadhyay ◽  
Srijana Subba ◽  
Ashis Kumar Saha ◽  
Biswanath Mukhopadhyay

Abstract Background Gall bladder carcinoma (GBC) is the most common malignancy of the biliary tract. Being known for its geographical and racial variations, and compared with the global statistics, its incidence is higher in the Indian subcontinent, mainly in the northern and eastern regions, accounting for 80 to 95% of cases. Aims and Objectives This study was conducted to evaluate the clinic-pathological spectrum and expression of EGFR and HER-2/NEU in GBCs and to understand their relation to prognosis, paving the way for targeted therapies for better treatment outcomes and patient survival. Materials and Methods This is a prospective study performed in a tertiary care hospital in 30 resected specimens of GBC cases recorded in our Department of Pathology from November 2017 to November 2019. Clinical history including the radiological reports and demographic parameters were included in the study pro forma. Immunohistochemical (IHC) staining for EGFR and HER-2/NEU was performed on all the selected cases. Clinicopathologic parameters like age, sex, histologic type, perineural, and lymphovascular invasion were compared and correlated with EGFR and HER-2/NEU status. Results Expression of EGFR was found in 93.33% of cases, which showed a highly significant correlation with histological tumor type (p = 0.000). HER-2/NEU expression was found in 56.66% of cases, which also showed a significant correlation with histological tumour type (p = 0.021). We found most of the cases with strong EGFR immunoreactivity (3+) were poorly differentiated tumors and most of the cases showing weak immunoreactivity for EGFR (1+) were well-differentiated. Conversely, in case of HER-2/NEU immunoreactivity, strong staining (3+) was seen in well-differentiated tumors and weak staining (1+) in poorly differentiated tumors. A significant correlation was also found between EGFR and HER-2/NEU expression (p = 0.000) and between cholelithiasis and EGFR expression (p = 0.033). Conclusion EGFR is expressed in most cases of GBC. Its expression is more in poorly differentiated carcinomas as compared to the well-differentiated carcinomas, whereas HER-2/NEU expression is more in well-differentiated carcinomas. Therefore, they may serve as independent prognostic factors and also as targets for molecular therapy in GBCs.


2006 ◽  
Vol 22 (5-6) ◽  
pp. 309-316 ◽  
Author(s):  
Jong-Shiaw Jin ◽  
Chi-Ying Wu ◽  
Yeh-Feng Lin ◽  
Jia-Yi Wang ◽  
Cheng-Ping Yu ◽  
...  

Aim: Extracellular matrix metalloprotease inducer (EMMPRIN) expression was demonstrated in several cancers, but its expression profile in colorectal cancers remains unclear. Epidermal growth factor receptor (EGFR) was reported to regulate EMMPRIN expression in human epithelial cancers. Our purpose was to determine EMMPRIN expression and its relationship with EGFR in colorectal cancers.Methods: Immunohistochemical analysis of EMMPRIN and EGFR was performed in tissue microarray slides of 90 surgical specimens including 32 well differentiated, 35 moderately differentiated, and 23 poorly differentiated colorectal adenocarcinomas.Results: All colorectal adenocarcinomas showed significant immunohistochemical expression of EMMPRIN. The EMMPRIN scores in poorly differentiated (303 ± 21) and moderately differentiated (326 ± 17) colorectal adenocarcinoma were significantly higher than in well differentiated (166 ± 20) colorectal adenocarcinoma. EGFR expression was mainly on the cell surface of tumor cells and the immunostaining scores of EGFR were significantly associated with the advanced clinical T and N stages. A significantly positive relationship between EMMPRIN and EGFR immunostaining scores was also noted.Conclusions: Increased expression of EMMPRIN and EGFR in colorectal adenocarcinomas is associated with clinicopathological parameters of advanced colorectal adenocarcinoma stages.In addition, the data from this study support the notion that EGFR expression may up-regulate EMMPRIN expression.


Author(s):  
Madhusmita Choudhury ◽  
Gargi Roy Choudhury ◽  
Monoj K. Deka ◽  
Shah A. Sheikh

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.


2018 ◽  
Vol 04 (01) ◽  
pp. 001-005
Author(s):  
Sachin Khanduri ◽  
Aakshit Goyal ◽  
Tarim Usmani ◽  
Shreshtha Jain ◽  
Arun Goyal ◽  
...  

Abstract Purpose: The present study was done with an aim to evaluate the usefulness of ultrasonography (USG) in early diagnosis of gall-bladder carcinoma for low-resource settings. Materials and Methods: A total of 264 clinically suspicious cases were enrolled in the study. The patients underwent USG followed by computed tomography (CT). Histopathological specimens were obtained from 208 cases. Final diagnosis was confirmed histopathologically/CT. Sensitivity, specificity, positive predictive, and negative predictive values of USG were calculated. Results: A total of 29 cases were confirmed as gall-bladder carcinoma, 58.6% were diagnosed at advanced stage (Stage III/IV). USG diagnosed 42 cases as neoplastic, however, 24 were true positive and 18 were false positive. USG was 82.8% sensitive and 92.5% specific. The positive and negative predictive values were 57.1% and 97.8%, respectively, diagnostic efficacy was 91.5%. 94.1% advanced stage gall bladder cancers were diagnosed correctly by USG. Sensitivity for early stages was promising (61.9%), however false positive was higher. Cost of USG was nearly five times lesser as compared to that of CT. Conclusion: USG was a useful economical imaging modality for the screening of gall bladder cancer in low-resource settings, especially for advanced stages. However, for early stages too, it seemed useful. We recommend to encourage the use of USG in early detection of gall-bladder carcinoma in socially and economically disadvantaged settings.


2021 ◽  
Vol 10 (10) ◽  
pp. 719-723
Author(s):  
Saurabh Rai ◽  
Chandra Shekhar ◽  
Osman Musa ◽  
Nisar Ansari ◽  
Rahul Agrawal ◽  
...  

BACKGROUND Gallbladder cancer is recognised as an irreversible malignancy with a high fatality rate. The highest incidence of gall bladder carcinoma is seen in India and Chile, and relatively low level in many Western countries. Gall bladder carcinoma has an extremely poor prognosis, increasing incidence, and diagnosed at an advanced stage despite recent advances in diagnostic modalities. Considering the high rate of mortality attributable mainly to late detection of disease at an advanced stage, early diagnosis remains to be one of the most important determinants of the outcome. This study was conducted to assess the role of tumour markers, namely carbohydrate antigen (CA 19-9), carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP) in the diagnosis of gall bladder carcinoma. We wanted to assess the diagnostic role of tumour markers in carcinoma gall bladder. METHODS Patients with radiologically and histopathologically confirmed diagnosis of carcinoma gall bladder were invited to participate in the study. A thorough history was taken, and relevant examination done as per protocol. All necessary laboratory and radiologic investigations were done according to study design. Assessment of the tumour markers CA19-9, CEA and AFP was done, and values compared with carcinoma gall bladder patients. RESULTS The diagnostic value of tumour markers has been studied in context with histopathological grade as all the cases were histopathologically proven cases of carcinoma gall bladder (Ca GB). CONCLUSIONS The present study showed that CA 19-9 was most effective with regard to its ability to differentiate between different grades of gall bladder carcinoma. KEY WORDS CA 19-9, CEA, AFP, Carcinoma Gallbladder


2020 ◽  
Vol 4 (3) ◽  
pp. 105-108
Author(s):  
Priti Meena ◽  
Vinant Bhargava ◽  
Devinder Singh Rana ◽  
Anil Kumar Bhalla ◽  
Ashwani Gupta ◽  
...  

Background: C3 glomerulopathy is caused by dysregulation of the alternative complement pathway. Association with solid organ tumors is rare. However, there have been a few case reports of membranoproliferative glomerulonephritis secondary to gastrointestinal neoplasms. Case: A 38-year-old female presented with abdominal distension, loss of appetite, amenorrhea, and easy fatigability. She had been diagnosed 8 months back with C3 glomerulopathy and had received immunosuppression. On evaluation, she was incidentally detected to have Krukenberg tumor. The primary site of malignancy was gall bladder. Conclusion: Our case report highlights a possible association between C3 glomerulopathy and Krukenberg tumor secondary to gall bladder carcinoma and emphasizes the fact that even in cases of C3 glomerulopathy, occult malignancy should be considered as an underlying pathology.


Author(s):  
Dharmpal Godara ◽  
Vijay Pal Singh Dhayal

Background: The present study highlights the occurrence of Incidental gallbladder carcinoma (IGBC) detected during histopathological examination in cholecystectomy specimens removed for cholelithiasis. Methods- This is a tertiary hospital based cross-sectional study of 500 cholecystectomy specimens removed during cholelithiasis. Relevant hospital records, histopathology slides and reports were reviewed, re-evaluated and studied. Results: 4(0.80%) cases of incidental gall bladder carcinoma (IGBC) were diagnosed from the histopathological evaluation (HPE) of 500 cholecystectomy specimens, constituting 0.80% of gall bladder specimens received during the study period. The age of the patients with IGBC ranged from 51-80 years. More females were affected than males with a M:F ratio of 1:3. Conclusion: Early detection of IGBC by histopathological examination would have a favourable impact on prognosis and management thereby increasing the survival outcome. Keywords: Cholelithiasis, Incidental Gall Bladder Carcinoma


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