The study on the carcinogenesis and tumor progression of esophageal carcinoma

在人类癌症中，RASSF1A经常因启动子甲基化而失活。为了了解RASSF1A基因在食管鳞状细胞癌（ESCC）中的作用，我们研究了原发性食管鳞状细胞癌中RASSF1A基因的甲基化，以确定这种表观遗传畸变的频率及其临床病理意义。采用甲基化特异性聚合酶链反应（MSP）检测55例ESCC DNA中RASSF1A基因的甲基化。55例原发性ESOC患者中有13例（24%）存在RASSF1A基因甲基化。未发现原发性ESCO中RASSF1A基因启动子甲基化与年龄、性别、定位、侵袭深度或肿瘤分期之间存在关联。发现与肿瘤分化有关。与预后无相关性。总之，我们认为启动子甲基化导致的RASSF1A基因失活与ESCC中肿瘤的去分化有关。组织金属蛋白酶3 （TII…More MP-3）抑制基质金属蛋白酶的活性，可能在肿瘤侵袭转移过程中发挥重要作用。我们研究了ESCC中TIMP-3减少与临床病理因素的关系。我们检查了从1983年至2001年间接受过手术的90例胸段食管癌患者身上取出的组织标本。采用标准链霉亲和素-生物素法进行免疫组化染色。TIMIP-3免疫染色可见于癌细胞和正常食管上皮细胞的细胞质中，特别是位于肿瘤浅部的细胞。90例患者中TIMP-3保留（+）、中度（+/-）和减少（-）的病例分别占30例、27例和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（P=0.003）、浸润性生长方式（P=0.003）、疾病分期（P=0.005）有显著相关性。TIMP-3（-）癌患者的生存率明显低于TIMP-3（+）和TIMP-3（+/-）癌患者（P=0.0003）。TIMP-3（+）、（+/-）和（-）患者的平均5年生存率分别为50%、58%和21%。综上所述，TIMP-3蛋白表达降低与侵袭活性和转移有关。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