The study on the carcinogenesis and tumor progression of esophageal carcinoma

RASSF 1A在人类癌症中经常因启动子甲基化而失活。为了了解RASSF 1A基因在食管鳞状细胞癌（ESCC）中的作用，我们研究了原发性ESCC中RASSF 1A基因的甲基化，以确定这种表观遗传畸变的频率和临床病理学意义。应用甲基化特异性聚合酶链反应（MSP）检测55例食管鳞癌组织中RASSF 1A基因甲基化状态。RASSF 1A基因甲基化在55例原发性ESOC中发现13例（24%）。原发性肝癌RASSF 1A基因启动子甲基化与年龄、性别、肿瘤部位、浸润深度、肿瘤分期无关。发现与肿瘤分化相关。与预后无相关性。总之，提示RASSF 1A基因启动子甲基化导致的失活与ESCC中肿瘤的去分化有关。 关于我们 MP-3抑制基质金属蛋白酶的活性，可能在肿瘤的侵袭和转移中起重要作用。我们研究了TIMP-3减少与ESCC临床病理因素之间的关系。我们检查了从1983年至2001年接受手术的90例胸段食管癌患者中取出的组织标本。免疫组化染色采用标准链霉亲和素-生物素法。TIMIP-3的免疫染色见于癌细胞和正常食管上皮细胞的细胞质中，特别是位于肿瘤浅区的细胞中。TIMP-3保留（+）、中度（+/-）和降低（-）的病例分别占90例患者中的30、27和33例（33、30、37%）。TIMP-3表达与肿瘤浸润深度（P=0.001）、淋巴结转移数目（P=0.003）、浸润性生长模式（P= 0.003）和疾病分期（P=0.005）显著相关。TIMP-3（-）组的生存率明显低于TIMP-3（+）组和TIMP-3（+/-）组（P=0.0003）。TIMP-3（+）、（+/-）和（-）患者的平均5年生存率分别为50%、58%和21%。总之，TIMP-3蛋白表达降低与侵袭活动和转移相关。这使得失去TIMP-3的癌症患者的预后明显不如维持TIMP-3的癌症患者。少

RASSF1A is frequently inactivated by promoter methylation in human cancers. To understand the involvement of the RASSF1A gene in esophageal squamous cell cancer (ESCC), we investigated the methylation of the RASSF1A gene in primary ESOC to define the frequency of this epigenetic aberration and the clinicopathological significance. Methylation-specific polymerase chain reaction (MSP) was used to detect RASSF1A gene methylation in DNA from 55 cases of ESCC. Methylation of the RASSF1A gene was found in 13 of 55 (24%) cases of primary ESOC. No association was found between the promoter methylation of the RASSF1A gene in primary ESCO and age, gender, localization, invasion depth, or tumor stage. Association was found with tumor differentiation. There was no correlation with its prognosis. In conclusion, it was suggested that an inactivation of the RASSF1A gene due to promoter methylation was associated with de-differentiation of the tumor in ESCC.Tissue inhibitor of metalloproteinase-3 (TII … More MP-3) inhibits the activity of matrix metalloproteinase, which may play an important role in carcinoma invasion and metastasis. We have investigated the relationship between TIMP-3 reduction and clinicopathological factors in ESCC. We examined tissue specimens that had been removed from 90 patients with thoracic esophageal cancer who had undergone surgery between 1983 and 2001. Immunohistochemical staining was performed by the standard streptavidin-biotin method. Immunostaining of TIMIP-3 was seen in the cytoplasm of cancer cells and normal esophageal epithelial cells, particularly in cells located in shallow areas of the tumour. TIMP-3 preserved (+), moderate (+/-), and reduced (-) cases accounted for 30, 27, and 33 of the 90 patients, respectively (33, 30, 37%). Significant correlations were observed between TIMP-3 expression and depth of tumour invasion (P=0.001), number of lymph node metastases (P=0.003), infiltrative growth pattern (P=0.003), and disease stage (P=0.005). The survival rates of patients with TIMP-3 (-) cancer were significantly lower than those of patients with TIMP-3 (+) and TIMP-3 (+/-) cancer (P=0.0003). The mean 5-year survival rates of patients with TIMP-3 (+), (+/-), and (-) were 50, 58, and 21%, respectively. In conclusion, decreased expression of TIMP-3 protein correlates with invasive activity and metastasis. This makes the prognosis for patients with cancer that has lost TIMP-3 significantly less favorable than that for patients with cancer that has maintained TIMP-3. Less