Evaluation of HER-2/neu status in Gastric Carcinoma

INTRODUCTION: Gastric carcinoma is the fourth most commonly diagnosed cancer in the world and is the second leading cause of cancer related death. In the West, the incidence is spontaneously declining for unknown reasons. In Asia it is still one of the commonest cancers accounting to around 13% of all malignancies. In countries like Japan and Korea in Eastern Asia, it accounts for 56% of all malignancies. Early diagnosis is challenging because of absence of symptoms in this stage of disease. More than 50% of patients with gastric cancer present in advanced, unresectable stages, making cure impossible. Two-thirds of these patients who undergo radical surgery will experience. Systemic treatment is the only option for the patients presenting in advanced stages. The median survival after diagnosis of metastatic disease is approximately 10-11 months with currently available therapies. Despite the introduction of multimodality treatment, neoadjuvant chemotherapy, postoperative chemoradiation and new chemotherapeutic regimens, there is only a minimal impact on the relapse free survival and overall survival of these patients. Many single agents and combination chemotherapeutic agents are active in the treatment of metastatic disease. Objective response rates ranging from 10% to 30% for single-agent and 30% to 60% for combination regimens have been reported. Although a large number of chemotherapy regimens are available, there is still no internationally accepted standard of care. Survival of patients presenting with advanced gastric cancer is still only 4%-10% at five years. Newer therapies are urgently needed for their better outcome. Recently, understanding of the molecular basis of cancer has contributed to the development of rationally designed molecular targeted therapies, which interfere with signalling cascades involved in cell differentiation, proliferation, and survival, of which EGFR plays an important role. Trastuzumab is one of the targeted drugs against EGFR2 (commonly known as HER-2/neu) and has recently shown to increase survival in patients with metastatic gastric carcinoma when given along with combination chemotherapy. Recent evidence suggests that patients diagnosed with metastatic gastric cancer should have the HER-2/neu status of their tumors to get benefit from treatment with Trastuzumab in combination with chemotherapy in case of HER-2/neu positivity. We conducted, this study to analyse the prevalence and significance of HER-2/neu over expression in patients with gastric carcinoma. AIM OF THE STUDY: The aim of this study: 1. To assess HER-2/neu overexpression in gastric carcinoma patients. 2. To assess the correlation between HER-2/neu overexpression and clinico-pathologic characteristics. MATERIALS AND METHODS: The present study is a Prospective study conducted in the Department of Medical Oncology, Madras Medical College and Rajiv Gandhi Government General Hospital for a period of one year between January 2011 and December 2011. Informed written consent was obtained from all patients prior to the start of the study. Institutional Ethics committee approval was obtained at the start of the study. Inclusion criteria: 1. Patients aged 18-65 years with gastric carcinoma proven by histopathology. 2. Adenocarcinoma by histology. Exclusion criteria: Histologies other than adneocarcinoma. METHODS: All selected patients underwent diagnostic upper gastrointestinal endoscopy. A CT scan of abdomen was done for all patients as staging procedure. The AJCC TNM cancer staging 7th edition was used for staging. Of the 50 samples evaluated, 25 were endoscopic specimens and 25 were post gastrectomy specimens. RESULTS: A total of 50 patients were included in this study. Various clinicopathologic characteristic features like age, sex, histopathological type and grade were analysed for association with Her-2/neu gene overexpression. IHC SCORE: Out of 50 patients, 10 (20%) were 3+, 3 patients (6%) had 2+, 10 patients (20%) had 1+ and 27 patients (54%) had 0 score by IHC. SUMMARY: The study titled “Evaluation of HER-2/neu status in Gastric Carcinoma” was a prospective study of 50 patients with newly diagnosed Gastric Carcinoma, admitted in the Department of Medical Oncology, Rajiv Gandhi Government General Hospital, Chennai. Eligible patients underwent clinical examination, endoscopy, CT Abdomen and Surgery if feasible. All patients underwent HER-2/neu status assessed in the histopathological specimen obtained by endoscopic biopsy or post gastrectomy specimen. The correlation between HER-2/neu status overexpression and clinicopathological features was analysed. There was no significant association between HER-2/neu status and clinicopathological features. CONCLUSION: The following conclusions were made from this study 1. Patients in this study presented at younger age than quoted in the western population. 2. The prevalence of HER-2/neu overexpression was 20% in this study population. 3. HER-2/neu overexpression was not associated with any major clinical or pathological features. 4. Since targeting HER-2/neu has shown an overall survival benefit of 2.7 months in literature, it can be recommended that all patients with newly diagnosed gastric cancer should undergo HER-2/neu testing for subsequent treatment with anti HER-2/neu therapy