Analysis in Carcinoma Stomach Her-2/neu Positivity by Immuno-histochemistry

Abstract

INTRODUCTION: Carcinoma stomach remains the leading cause of death in both developed and developing countries with mortality ranks second in the world. Early stages of tumour are amenable to surgical correction, but usually the patients presents in advanced stage with signs of inoperability. Inspite of newer modalities of therapies available for treatment, survival rate is poor in advanced stage. The genesis of molecular biology led to the development of newly designed therapeutic molecules, which interferes with the pathogenesis of cancer cells. The Human epidermal growth receptor 2 gene (Her-2, otherwise called as ERBB 2 and Her-2 nu) is now considered as the cornerstone in solid human cancers, especially gastric cancer. There is now a strong correlation that exists between Her-2 overexpression and poor outcome in gastric cancer patients, which has been evidenced by many international studies. Most of the studies regarding Her-2 is from the foreign literature. This study is an attempt to analyse Her-2 positivity in gastric carcinoma patients at Madurai Government Rajaji Hospital which primarily caters the rural population in and around Madurai. AIMS & OBJECTIVES: 1. To assess Her-2/neu content in our gastric cancer patients. 2. To assess the correlation between this receptor tumour content and clinicopathologic characteristics. METHODS AND MATERIALS: Thirty gastric adenocarcinoma patients paraffin block was obtained from Department of Pathology, Madurai Medical College. It consists of both surgical and biopsy block. All patients had undergone supra and infra diaphragmatic imaging studies with chest X-ray, Ultrasound abdomen, CT abdomen and chest. TNM staging had been performed on all patients according to American Joint Committee on Cancer. Ten patients undergone surgery followed by chemotherapy and remaining twenty patients were receiving palliative chemotherapy. Representative blocks were chosen for immunostaining. IHC was performed with Hercep test kit. Tumour with more than ten percent of cancer cells showing membranous staining for Her-2 were classified as positive. RESULTS: Out of 30 patients, Her 2 positivity reported was 7. Among seven patients, maximum positivity was seen in age group between 41 to 60, this is because maximum number of cases were reported in these age groups. The P value was 0.695 which was not statistically significant on comparing with other age groups. Of the 30 patients, male to female ratio was 2.75.this is because cancer stomach is more common in males on compared to females Among 22 males, 5 showed positivity and among 8 females, 2 showed positivity, the ratio was 2.5. The P value was 1.000 which was not statistically significant. Also on comparing males and females individually with positive and negative results to their total, P value obtained was 0.063 (males) and 0.464 (females) which was not significant. Out of 30 patients, all three types of grade were almost equally present. Among 7 positive patients, maximum cases belong to moderate differentiation, on comparing with other two, the P value was 0.494 which was not statistically significant. CONCLUSION: Gastric cancer is one of the leading causes of cancer mortality in INDIA. This is due to the fact that most of the patients were diagnosed at end stage where only palliation is possible. In patients where surgical resection is not possible, systemic chemotherapy is the main treatment option. Although many chemotherapeutic regimes have been extensively studied both as monotherapy and combination therapy active in metastatic diseases, there is no internationally accepted standard of care and survival remains poor. In order to increase the life span newer therapeutic strategies are needed. There is increasing evidence that HER2 overexpression in patients with gastric cancer is correlated with poor outcomes and more aggressive disease. Various trials showed TRASTUZUMAB inhibits the growth of human gastric cancer in patients with HER2 overexpression both in vitro and vivo. These clinical trials paved way for starting ToGA trial which was studied in gastric cancer patients conducted in various countries all over the world. The results of these studies will contribute to a better knowledge of the efficacy and treatment of TRASTUZUMB- based therapy in HER2 POSITIVE gastric cancer in the future

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