Overexpression of heparanase multiple antigenic peptide 2 is associated with poor prognosis in gastric cancer: Potential for therapy.

Tumor-associated antigens (TAAs) trigger a TAA-specific immune response, thus they are the crux of antitumor immunosurveillance. A major advance in tumor immunology in the last 20 years was marked by the verification that CTL or B-cell epitopes rather than integral TAAs induce immunoreactivity. Previous studies on the correlation between heparanase (Hpa) expression and clinical or pathological features have generally used commercial antibodies against full-length Hpa protein rather than the functional epitopes, and the antigen determinants of such antibodies have not yet been defined. In our investigation of Hpa peptide expression in gastric cancer tissues and its association with tumor invasion, metastasis and prognosis, we analyzed Hpa expression in the tissues of 132 patients with gastric cancer using tissue microarray (TMA) technology and immunohistochemical staining. Three self-developed rabbit polyclonal antibodies against Hpa multiple antigenic peptides (MAP) and one commercial polyclonal rabbit antibody against the 50-8 kDa Hpa heterodimer were used. Clinical and pathological significance was evaluated using the Chi-square test and Kaplan-Meier survival curve analysis. The results demonstrated that the positivity rates using the antibody against MAP2 and the commercial antibody were 60.6% (80/132) and 65.2% (86/132), respectively. No expression of either MAP1 or MAP3 was noted in the cancer tissues of the 132 cases. MAP2 behaved in a similar manner to the commercial antibody in that a higher Hpa expression was observed in the cancer tissues with vessel invasion, serosal involvement, distant metastasis, poor differentiation and TNM stages III and IV. Moreover, the patients with a positive Hpa expression had a far poorer prognosis, with lower one-year and five-year survival rates. Our results demonstrate that in a similar manner to full-length Hpa proteins, MAP2 expression is closely associated with the invasion, metastasis and prognosis of gastric cancer. This finding may be of potential use in clinical therapy and in estimating the prognosis of a tumor.