Zhang Jun, Yang Jianmin, Han Xiaomei, Zhao Zhongsheng, DU Ling, Yu Tong, Wang Huiju
Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
Oncol Lett. 2012 Jul;4(1):178-182. doi: 10.3892/ol.2012.703. Epub 2012 May 4.
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.
肿瘤相关抗原（TAAs）引发TAA特异性免疫反应，因此它们是抗肿瘤免疫监视的关键。过去20年肿瘤免疫学的一项重大进展是证实细胞毒性T淋巴细胞（CTL）或B细胞表位而非完整的TAAs诱导免疫反应性。以往关于乙酰肝素酶（Hpa）表达与临床或病理特征之间相关性的研究，通常使用针对全长Hpa蛋白而非功能性表位的商业抗体，且此类抗体的抗原决定簇尚未明确。在我们对胃癌组织中Hpa肽表达及其与肿瘤侵袭、转移和预后关系的研究中，我们使用组织芯片（TMA）技术和免疫组织化学染色分析了132例胃癌患者组织中的Hpa表达。使用了三种自行研制的针对Hpa多抗原肽（MAP）的兔多克隆抗体和一种针对50 - 8 kDa Hpa异二聚体的商业兔多克隆抗体。采用卡方检验和Kaplan - Meier生存曲线分析评估临床和病理意义。结果表明，使用针对MAP2的抗体和商业抗体的阳性率分别为60.6%（80/132）和65.2%（86/132）。在132例病例的癌组织中未观察到MAP1或MAP3的表达。MAP2的表现与商业抗体相似，即在伴有血管侵犯、浆膜受累、远处转移、低分化以及TNM分期为III期和IV期的癌组织中观察到更高的Hpa表达。此外，Hpa表达阳性的患者预后差得多，一年和五年生存率较低。我们的结果表明，与全长Hpa蛋白类似，MAP2表达与胃癌的侵袭、转移和预后密切相关。这一发现可能在临床治疗和评估肿瘤预后方面具有潜在用途。
