Expression of Id proteins in human hepatocellular carcinoma: relevance to tumor dedifferentiation.
Expression of Id proteins in human hepatocellular carcinoma: relevance to tumor dedifferentiation.
复制标题
DOI：
10.3892/ijo.26.2.319
复制
发表时间：
2005-02
影响因子：
5.2
通讯作者：
B. Damdinsuren;H. Nagano;M. Kondo;Hirofumi Yamamoto;N. Hiraoka;Tameyoshi Yamamoto;S. Marubashi;A. Miyamoto;K. Umeshita;K. Dono;S. Nakamori;K. Wakasa;M. Sakon;M. Monden
中科院分区：
文献类型：
--
作者：
B. Damdinsuren;H. Nagano;M. Kondo;Hirofumi Yamamoto;N. Hiraoka;Tameyoshi Yamamoto;S. Marubashi;A. Miyamoto;K. Umeshita;K. Dono;S. Nakamori;K. Wakasa;M. Sakon;M. Monden
Id（Inhibitor of DNA binding or Differentiation）蛋白是一类螺旋-环-螺旋（helix-loop-helix）转录因子，在细胞分化、细胞周期和血管生成中发挥重要作用。然而，Id蛋白在肝细胞癌（HCC）中的作用仍不清楚。我们检测了54例手术切除的HCC中Id 1、Id 2和Id 3蛋白的免疫组化表达，其中30例伴有HCV或HBV相关慢性肝炎（n=30），24例肝硬化（n=24）。所有非癌性肝组织均呈Id蛋白免疫反应性，且表达从慢性肝炎到肝硬化逐渐增加。在HCC（n=45）中，高分化的肿瘤大多对所有Id蛋白表现出强或中等的免疫染色，而弱表达或无表达的样品的比例随着肿瘤去分化而增加，并且经常在低分化（Id 1，2，3分别为66.7%，93.3%和93.3%）或未分化（所有Ids均为100%）的HCC中观察到。临床病理学研究显示Id 1、2和3的表达与癌的分化程度显著相关（p分别为0.0044、0.0014和0.0014），尽管单因素分析表明Id 1的高表达是患者无病生存期较长的显著预测因素（p=0.047）。在Id 2和Id 3中也观察到类似的趋势。目前的研究表明，高分化肝癌和低表达在先进的去分化肝癌的Id 1，2和3的高表达，在乳腺癌，前列腺癌和结肠癌的发生过程中，其连续表达。这些结果表明，Id 1，2和3可能在肝癌发生的早期阶段发挥作用，而不是在晚期癌的发展，因此可能与肝癌去分化。
Several studies reported that Id (Inhibitor of DNA binding or Differentiation) proteins, helix-loop-helix transcription factors, have important roles in differentiation, cell cycle and angiogenesis in various cells. However, the role of Id proteins in hepatocellular carcinoma (HCC) remains unclear. We examined the immunohistochemical expression of Id1, Id2 and Id3 proteins in 54 surgically resected HCCs with surrounding HCV or HBV-related chronic hepatitis (n=30) and liver cirrhosis (n=24). All non-cancerous livers exhibited immunoreactivity for Id proteins and the expression increased from chronic hepatitis to cirrhosis. In HCCs (n=45), well-differentiated tumors mostly exhibited strong or moderate immunostaining for all Id proteins, while proportion of the samples with weak or no expression increased with tumor dedifferentiation and frequently observed in poorly (66.7, 93.3 and 93.3% respectively for Id1, 2, 3) or undifferentiated (100% for all Ids) HCCs. Clinicopathological survey demonstrated a significant correlation between Id1, 2 and 3 expression and differentiation of carcinoma (p=0.0044, 0.0014 and 0.0014, respectively) although univariate analysis indicated that high expression of Id1 was significant predictive factor for longer disease-free survival of the patients (p=0.047). A similar tendency was also observed with Id2 and Id3. The present study demonstrate high expression of Id1, 2 and 3 in well-differentiated HCC and low expression in advanced dedifferentiated HCC, in contrast to its continuous expression during breast, prostate and colon carcinogenesis. These findings suggested that Id1, 2 and 3 might play a role in the early stages of hepatocarcinogenesis, but not in the development of advanced carcinoma, and might consequently be related to HCC dedifferentiation.