Established clinico -pathological factors can place patients with breast cancer into good and poor prognostic categories, but even within these groups behaviour and response to treatment can differ. This study examined the value of cell cycle and apoptotic regulatory proteins in predicting behaviour in a poor prognostic group. A total of 165 patients, all of whom had died of breast cancer with duration of survival 12 -127 months, median 38 months, were examined using immunohistochemistry for proliferation, apoptosis, p53, phosphorylated p53, p21, checkpoint kinase 2 (Chk2), bcl-2, bax, survivin and XIAP. All had received chemotherapy and/or hormonal therapy and were predominantly T2, node positive, grade III with only half oestrogen-receptor (ER) positive. High proliferation, phosphorylated p53, Chk2 and survivin expression correlated with grade III and lack of ER, whereas low proliferation, p21 and bcl-2 related to better grade and presence of ER. On univariate analysis grade, proliferation, phosphorylated p53, bcl-2, ER and survivin related to duration of survival. In multivariate analysis, grade (P ¼ 0.001) and survivin (P ¼ 0.005) were independent prognostic factors, grade III and presence of survivin relating to shorter survival. The latter was particularly for those patients receiving neoadjuvant therapy and adjuvant chemo-and hormonal therapy. The presence of the inhibitor of apoptosis protein survivin is a highly significant independent predictor of shorter duration of survival of patients with poor prognostic features, and merits investigation as a marker in other prognostic groups.
Background Gastric cancer (GC) still represents a major health problem, despite a decrease in its incidence in the last few years. Because of the social impact of GC, there is a need for developing novel biomarkers to stratify patients into appropriate screening, surveillance, or treatment programs. Although histopathology remains the most reliable and less-expensive method, numerous efforts have been made toward identifying and validating novel biomarkers. Recent advances in molecular therapy have identified human epidermal growth factor receptor 2 (HER2) as an important target for anticancer therapy in GC. Although the clinical relevance and prognostic significance of HER2 in breast cancer have been well acknowledged, it remains controversial in GC. The aim of this work was to evaluate the role of HER2 as a prognostic factor in patients with GC.Methods HER2 expression was investigated in 30 patients with GC by immunohistochemical staining and the results were compared and correlated with clinicopathologic parameters (age, sex, tumor location, histopathological type tumor stage, lymphovascular invasion, and lymph node metastasis).Results Among the samples that attained a score of 3 + , 85% showed staining in 50% or more of the tumor area, 10% that attained a score of 2 + showed staining in 50% or more of the tumor area, whereas only 5% that attained a score of 1 + showed staining less than 50%. There was no statistically significant correlation between HER2 positivity and age (P = 0.0601), sex (P = 0.3000), or tumor location (P = 0.364). HER2-positive tumors were found more often in lesions located in the lower third of the stomach compared with those located in the upper third (83 vs. 71%). According to Lauren's classification, HER2 overexpression was more often detected in the intestinal histological type (93%) than in the mixed (83%) or diffuse (67%) type, although this difference was not statistically significant. HER2 positivity was statistically significantly correlated with tumor-node-metastasis stage (P = 0.0312) and lymph node metastasis (P = 0.009).Conclusion HER2 overexpression was positively correlated with aggressive biological behavior and was an independent poor prognostic factor for GCs. Therefore, HER2-positive GCs should be considered for adjuvant trastuzumab therapy.
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