Prognostic value of immunohistochemical marker HER2/neu in patients resected for gastric cancer stage IIIA

Abstract

IntroductionPatients with the same stage of malignancy often have different life-span, which makes it necessary to search for new prognostic factors.The high incidence and low survival rate of patients with gastric cancer also cause an increased interest in studying the immunohistochemical profile of tumors of the stomach. Recently, researchers are studying the prognostic significance of immunohistochemical markers such as: EGFR [10], VEGF [12,15,18], HER2/neu [8,17,19], expression of betakatenin [1], hERG1 [7], p53 [14], PCNA [14,20]Of particular interest is the HER2/neu. Overexpression of HER2/neu promotes tumor growth and plays an important role in the pathogenesis of some human malignancies [17].Nevertheless, the impact of HER2/neu status on the prognosis of patients with gastric cancer remains controversial [6,11,19]. Nakajima Garcia and colleagues believe that the increased expression of HER2/neu in patients with gastric cancer correlates with poor prognosis and more aggressive disease [11]. At the same time, Begnami found that life expectancy in gastric cancer patients with HER-2/neu-positively stained tumors was significantly shorter than in patients with HER-2/neu-negatively stained tumors (17 months vs. 40 months, respectively, p=0.023) [5].The aim of researchStudy the prognostic significance of immunohistochemical marker HER-2/neu in patients resected for gastric cancer stage IIIA.Materials and methodsMaterials for the study were histologic surgical specimens of the primary tumor in 21 patients who had surgery in the Zaporozhye Regional Clinical Oncology Center due to stomach cancer stage IIIA, including 14 men (67%) and 7 females (33%).Patients underwent surgery in the volume: gastrectomy and distal subtotal resection, 86% of patients received adjuvant chemotherapy of standard schemes.Immunohistochemical study of HER2/neu (erbB-2) used a rabbit polyclonal antibody. Immunohistochemical reaction was evaluated as negative in the absence of expression of membrane receptors or HER2/neu coloring immunopositive less than 5% of tumor cells ("-" - no reaction) as low positive - in the presence of 6-10 % of tumor cells immunopositive ("+"), moderately positive - 10-50% ("++") and high pozitive - 50% positive tumor cells ("+++"). For further comparative immunohistochemical study identified two main levels of immunoreactivity: low or reduced protein expression (-/+) and high level or overexpression of the marker (++/+++).To assess survival used the Kaplan - Meier. Comparison of survival curves was performed using the Cox-F test.ResultsThe largest group of patients with gastric cancer stage IIIA consisted of patients with a negative reaction to the presence of receptor HER2/neu (47,6%), the second place is a group of patients with moderately positive reaction - 23.8%, patients with low positive and high pozitive reactions were equally divided - by 14.3%.Median survival of patients with gastric cancer stage IIIA was 19.8 months.The study two groups of patients with a low level or reduced protein expression (-/+) and high level or overexpression of the marker (++/+++) showed a higher survival rate in the former group (median survival was 50 months) compared to the second group, where the median was equal to 16 months (p<0.05).Conclusion1. Median survival of patients with gastric cancer operated stage IIIA was on average 19.8 months.2. High level or overexpression of marker HER2/neu (++/+++) is bad prognostic sign for life expectancy of patients with stage IIIA (p<0.05).3. The prospect of further study is research of the prognostic value of marker HER2/neu in patients with gastric cancer stages I and II.