Expression and prognostic significance of E Cadherin, EGFR, p53 and HER-2/NEU in Gastric Carcinoma.

Tharageswari, S (2013) Expression and prognostic significance of E Cadherin, EGFR, p53 and HER-2/NEU in Gastric Carcinoma. Masters thesis, Madras Medical College, Chennai.

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Abstract

Stomach cancer is the fourth most common cancer worldwide (1). It is a disease with a high death rate (~700,000 per year) making it the second most common cause of cancer death worldwide after lung cancer(2). It is more common in men than in women with a ratio of 1.6:1(1, 3). It is a disease of middle aged and elderly with a peak incidence at around 65 years (1). Although a steady decline in the incidence of gastric carcinoma has been noted worldwide, the absolute number of new cases per year is increasing mainly because of the aging population. Decline in incidence rate is seen in the western countries (4). In Asia it is still one of the most common malignancies accounting for 18% of all malignancies. In countries like Japan and Korea it accounts for 56% of malignancies (5). More than 50% of cases present in advanced unresectable stages making cure impossible. The overall 5 year survival rate is 28% irrespective of the stage at which the patient presents. The morphological and histological types of gastric carcinomas are variable and they may not correlate well with the prognosis. The prognosis is mainly dependant on the clinical stage of the disease. But even within a specific stage, there is variability in prognosis from patient to patient. There has been a constant search for specific biological markers to identify the subgroups of patients with more aggressive course of the disease (6). E Cadherin, EGFR, p53 and HER-2/Neu have been proposed as potential tool for the evaluation of prognosis of gastric cancer. E Cadherin plays a crucial role in cell- cell adhesion in epithelial tissues. The decreased E Cadherin expression correlates with dedifferentiation, infiltrative tumour growth, distant metastasis, and poor survival for patients with certain carcinomas. Epidermal Growth Factor Receptor (EGFR) is a transmembrane tyrosine kinase receptor, and is one of the members of EGFR family of receptors. This receptor activation causes stimulation of the downstream signaling pathway that regulates cell proliferation, migration, adhesion, differentiation and survival. Gene amplification and ⁄ or protein over expression of EGFR have been observed in a variety of solid tumours. p53 is a tumour suppressor gene which negatively regulates cell cycle. A loss of function mutation in p53 gene results in enhanced proliferative activity and tumour progression. In contrast to the normal p53 protein, the mutated p53 protein has an increased half-life and hence accumulates within the cell nucleus. This can be detected immunohistochemically using monoclonal antibodies. CONCLUSION : The incidence of gastric carcinoma in the year 2011 in RGGGH was 3.26%. Many patients were older than 55 years of age with male preponderance which is similar to several other studies conducted throughout the world. Females showed a younger mean age of incidence compared to males. 29% of cases showed reduced expression of E Cadherin. A significant association was found between reduced expression of E Cadherin and reduced survival. A significant association of EGFR over expression was found with moderately differentiated grade. No significant association was found between EGFR expression and survival. An increased frequency of cases with p53 positivity showed intestinal type of Lauren‘s classification, moderately and poorly differentiated grades and no association between p53 positivity and survival was found. All the cases which showed HER-2/Neu over expression showed T3 level of infiltration, no association with HER- 2/Neu expression and survival was found. To conclude, identifying the expression of E Cadherin, EGFR, P53 and HER-2/Neu in gastric carcinoma can help to identify patients with reduced survival and to identify eligible candidates for targeted therapy. A larger sample size and follow up for a longer period might shed more light on the role of the above markers in gastric carcinoma.

Item Type: Thesis (Masters)
Uncontrolled Keywords: Expression ; prognostic significance ; E Cadherin ; EGFR ; p53 ; HER-2/NEU ; Gastric Carcinoma.
Subjects: MEDICAL > Pathology
Depositing User: Subramani R
Date Deposited: 29 Jun 2017 11:25
Last Modified: 29 Jun 2017 11:25
URI: http://repository-tnmgrmu.ac.in/id/eprint/398

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