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G1-S调节因子在肝内胆管细胞癌中的表达及临床意义

Expression and clinical significance of the G1-S modulators in intrahepatic cholangiocellular carcinoma.

作者信息

Ito Y, Takeda T, Sasaki Y, Sakon M, Yamada T, Ishiguro S, Imaoka S, Tsujimoto M, Matsuura N

机构信息

Department of Surgery, Osaka Seamen's Insurance Hospital, Osaka, Japan.

出版信息

Oncology. 2001;60(3):242-51. doi: 10.1159/000055325.

DOI:10.1159/000055325
PMID:11340376
Abstract

OBJECTIVE

To elucidate the clinical roles of G1-S modulators in cholangiocellular carcinoma (CCC).

METHODS

We performed immunohistochemistry using antibodies against the retinoblastoma gene product (pRb), p16, p21, p27, p53 and cyclin D1 for 41 cases of CCC as well as normal bile ducts.

RESULTS

The p27 labeling index (LI) was significantly higher in cases without lymph node metastasis than in normal bile ducts, but it decreased greatly in cases with lymph node metastasis. It was inversely related to the Ki-67 LI. The p16 LI also showed a relationship with lymph node metastasis, but not with the Ki-67 LI. The p21 LI was even higher in poorly differentiated cases and showed a direct relationship with the Ki-67 LI, although it is a negative regulator of the cell cycle. pRb expression did not correlate with any clinicopathological features. Cyclin D1 overexpression was more frequently observed in cases with poor or moderate differentiation and with lymph node metastasis. Cyclin D1 overexpression and aberrant p53 expression showed direct relationships with the Ki-67 LI.

CONCLUSIONS

These results suggest that in CCC: (1) p27 expression reflects the biological character of the carcinoma and may regulate its progression; (2) cyclin D1 plays a crucial role in cell cycle progression, and (3) aberrant p53 expression has some effect on CCC cell proliferating activity.

摘要

目的

阐明G1-S调节因子在胆管细胞癌(CCC)中的临床作用。

方法

我们使用抗视网膜母细胞瘤基因产物(pRb)、p16、p21、p27、p53和细胞周期蛋白D1的抗体,对41例CCC病例以及正常胆管进行免疫组织化学检测。

结果

无淋巴结转移病例的p27标记指数(LI)显著高于正常胆管,但在有淋巴结转移的病例中大幅下降。它与Ki-67 LI呈负相关。p16 LI也与淋巴结转移有关,但与Ki-67 LI无关。p21 LI在低分化病例中更高,并且与Ki-67 LI呈正相关,尽管它是细胞周期的负调节因子。pRb表达与任何临床病理特征均无相关性。细胞周期蛋白D1过表达在中低分化及有淋巴结转移的病例中更常见。细胞周期蛋白D1过表达和p53异常表达与Ki-67 LI呈正相关。

结论

这些结果表明,在CCC中:(1)p27表达反映了肿瘤的生物学特性并可能调节其进展;(2)细胞周期蛋白D1在细胞周期进程中起关键作用;(3)p53异常表达对CCC细胞增殖活性有一定影响。

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