Abe N, Watanabe T, Sugiyama M, Uchimura H, Chiappetta G, Fusco A, Atomi Y
First Department of Surgery, Kyorin University School of Medicine, Mitaka City, Tokyo, Japan.
Cancer Res. 1999 Mar 15;59(6):1169-74.
High mobility group I(Y) [HMGI(Y)] proteins are architectural factors abundantly expressed during embryogenesis, and their overexpression is known to be closely associated with neoplastic transformation of cells. This study was performed to investigate whether determination of HMGI(Y) expression level could assist in (a) differential diagnosis between colorectal carcinoma, adenoma, and normal tissue and (b) determination of the prognosis of patients with colorectal cancer. To this end, HMGI(Y) expression was determined at both the protein and mRNA levels in 30 colorectal carcinomas, 26 adenomas, and 23 normal mucosa samples, and further correlations between the protein expression levels and various clinicopathological parameters, such as depth of tumor invasion, lymphatic and/or venous involvement, regional lymph node metastasis, and Dukes' stage, were determined in 30 carcinoma cases. The expression of HMGI(Y) proteins was significantly increased in carcinoma and adenoma with severe atypia compared with that in adenoma with less atypia and normal colorectal mucosa. This increase in HMGI(Y) protein expression was found to be because of an increase in its mRNA expression by RNA in situ hybridization analysis. Clinicopathological analysis revealed that the level of HMGI(Y) protein expression was significantly correlated with parameters known to be indicative of a poor prognosis in colorectal cancer patients. These findings indicate that the determination of the HMGI(Y) protein expression level could be a potential marker for the diagnosis of colorectal neoplasias and can be of great value in predicting the prognosis of patients with colorectal cancer.
高迁移率族蛋白I(Y)[HMGI(Y)]是在胚胎发育过程中大量表达的结构因子，已知其过表达与细胞的肿瘤转化密切相关。本研究旨在探讨测定HMGI(Y)表达水平是否有助于(a)结直肠癌、腺瘤和正常组织的鉴别诊断，以及(b)确定结直肠癌患者的预后。为此，在30例结直肠癌、26例腺瘤和23例正常黏膜样本中测定了HMGI(Y)在蛋白质和mRNA水平的表达，并在30例癌病例中进一步确定了蛋白质表达水平与各种临床病理参数之间的相关性，如肿瘤浸润深度、淋巴管和/或静脉受累、区域淋巴结转移和Dukes分期。与非典型性较轻的腺瘤和正常结直肠黏膜相比，HMGI(Y)蛋白在重度非典型性癌和腺瘤中的表达显著增加。通过RNA原位杂交分析发现，HMGI(Y)蛋白表达的增加是由于其mRNA表达的增加。临床病理分析显示，HMGI(Y)蛋白表达水平与已知提示结直肠癌患者预后不良的参数显著相关。这些发现表明测定HMGI(Y)蛋白表达水平可能是诊断结直肠肿瘤的潜在标志物，对预测结直肠癌患者的预后具有重要价值。
