Thus in order to evaluate the HER-2 expression, the Remmele scale (IRS) [15] modified by the authors and standardised Hercep test score modified for GC by Hofmann et al. were applied selleck chem inhibitor (Table 1) [16]. In IRS scale the intensity of color reaction and percentage of positive cells were taken into account. The score represented a product of points given for the evaluated characters and it ranged from 0 to 12 (Table 1). Cases with expression of 0 to 3 in IRS scale and with score 0 to 1+ according to Hofmann et al.’s criteria were treated as cases without overexpression (Table 2). It is well known that patients with gastric cancer have a heterogeneous HER-2 expression. Intratumoral heterogeneity of HER2 expression may potentially contribute to inaccurate assessment of HER2 status.
There is evidence that tumor heterogeneity is more common in gastric cancer (4.8%) than in breast cancer (1.4%) [16]. We observed 9% cases with heterogenous HER-2 immunoreactivity. Therefore, in some institutions the evaluation of HER-2 expression in the immunohistochemical staining is carried out using several sections of tissue sample. In our study single slide from large representative resection specimen for each cancer case was analyzed and 10% cutoff for the number of reactive cells was retained.Table 1Two procedures for evaluation of HER-2 expression.Table 2Parameters of HER-2 immunoreactivity.2.4. Statistical AnalysisStatistical analyses were performed using the Statistica 9.1 software (StatSoft Inc., Tulsa, OK, USA) and R language and environment for statistical computing (R Foundation for Statistical Computing, Vienna, Austria, http://www.
R-project.org/). Chi2 and Spearman rank correlation were used to analyze associations between immunohistochemical parameters of HER-2 Brefeldin_A expression and clinicopathological features. The overall survival rate was estimated by the Kaplan-Meier method. Multivariate analyses (Cox proportional hazard regression models) were also performed to assess the prognostic value of HER-2 expression and other clinicopathological features.3. Results3.1. HER-2 Expression in Gastric CancerThe HER-2 overexpression was detected in 23 (29.5%) tumors in Hercep test (IHC 2+/3+) and in 24 (30.7%) in IRS scale (IRS 4�C12) (Figure 1). Lack of HER-2 expression was found in 35 cases (44.9%). In all samples membrane localization of HER-2 in gastric cancer cells was dominantly observed, but cytoplasmic topography was also described (Table 2).Figure 1Immunohistochemical expression of HER-2 in gastric cancer tissue: (a) Hercept test: 1+, IRS: 4, ��200; (b) Hercep test: 2+, IRS: 8, ��200; (c) HercepTest: 3+, IRS: 12, ��200; (d) Hercep test: 3+, IRS: 12, ��200.3.2.