Venkatesh, B S (2014) A study on role of HER 2/NEU over expression in gastric carcinoma in south Indian population. Masters thesis, Stanley Medical College, Chennai.
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Abstract
INTRODUCTION: Adenocarcinoma of stomach, so called “Captain of men of death” was the leading cause of cancer related deaths through the most of the 20th century and as on now ranking second only next to lung cancer. Even though surgical resection is the mainstay treatment for early gastric cancer, most of the patients present to us in advanced stages where adjuvant chemoradiation comes into play. Survival of patients with advanced resectable/non resectable gastric cancer treated with chemotherapy still remains poor. So the role of novel therapies is warranted. Her 2/neu (human epidermal growth factor receptor 2) also called as erbB2 /cd340/p185 is a protein encoded by gene ERBB2, a member of EFGR/erbB family. Amplification or over expression of HER 2/NEU which acts as a proto oncogene has been demonstrated to play an important role as a bio marker and target of therapy in breast cancer. It has been demonstrated in recent western clinical trials, over expression of the same in gastric cancer too. But the frequency of expression differs in each geographical area and incidence of her 2 /neu in gastric cancer in south Indian population is not clear. Western studies indicate poor prognosis and poor response to chemotherapy in HER2/NEU over expressed cases of gastric cancer, but as on now, no study is clear in India. Trastuzumab is a monoclonal antibody which specifically targets HER2 protein by directly binding to extracellular domain of receptor and successfully used for breast cancer patients ,but not yet been tried in India for gastric cancer patients. This study may pave way for the introduction of trastuzumab in treating patients with advanced gastric malignancies and thereby enhance survival rates and improve the quality of life of those patients justifying the cost benefits. Since most of the patients coming to our hospital are poor and cannot afford costly drugs, the justification to start a treatment is warranted and this study may provide a justification. AIMS AND OBJECTIVES: 1. To know the incidence of HER2/NEU over expression in gastric cancer in our locality. 2. To study the staging , operability and prognosis of gastric cancer in relation to HER2/NEU expression. 3. To study the aggressiveness and histology of gastric cancer in relation to HER2/NEU expression. 4. To study the HER2/NEU expression based on locality of tumours. MATERIALS AND METHODS: Our hospital is a referral centre for gastro intestinal diseases with attached institute of surgical gastroenterology. Cases of carcinoma stomach were selected randomly from 2012 -2013: 1. Dept. Of general surgery (all 7 units), 2. Dept. of surgical gastroenterology, 3. Dept. of medical oncology, 4. Dept. of medical gastroenterology, 5. Endoscopy clinic. Samples were either in the form of endoscopy biopsy or gastrectomy specimens. Samples were collected after obtaining consent from the patient and transported to pathology lab via formalin or saline containers and tissue processing. The patients were given full knowledge of the study and explained its merits and demerits and obtained consent from them. Tissues were mounted on paraffin blocks. Then paraffin blocks were used for slide preparation one for routne histopathology thus determining its staging , grading and margin positivity whenever possible. The other slide is prepared for immunohistochemistry and subjected to immunohistochemistry. A thorough history and clinical examination obtained from the patient and evaluation done. CONCLUSION: There is a low prevalence of HER2/NEU positivity 6% in the population of gastric carcinoma patients studied. The low incidence can be explained by the difference in genetics in gepgraphical population or due to the diagnostic facility available. FISH could have helped more in identifying more positive cases. HER2/neu positivity occurred more in OG junction tumours 25% and hence can be used as prognostic indicator for OG Junction subtype cancers . The positivity for HER2/neu also indicates advanced gastric carcinoma and poor prognosis and occurred mostly in poorly differentiated diffuse carcinomas contradicting to previous studies published. This could be explained either as a result of small population studied or diagnostic facility availability. However, studies on larger population with hybridisation techniques is essential so that we could add more years to patients with poor prognosis and improve the quality of life. In a developing country like India, where use of trastuzumab should be cost effective for our patients, more studies are warranted in this area, so as to get the broader picture of the same.
| Item Type: | Thesis (Masters) |
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| Uncontrolled Keywords: | HER 2/NEU ; over expression ; gastric carcinoma ; south Indian population. |
| Subjects: | MEDICAL > General Surgery |
| Depositing User: | Devi S |
| Date Deposited: | 05 Jul 2018 03:44 |
| Last Modified: | 05 Jul 2018 17:50 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/8644 |
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