Elevated expression of P63 protein in human esophageal squamous cell carcinomas
Elevated expression of P63 protein in human esophageal squamous cell carcinomas
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DOI：
10.1002/ijc.10739
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发表时间：
2002-12-20
影响因子：
6.4
通讯作者：
Wang, MR
中科院分区：
文献类型：
--
作者：
Hu, H;Xia, SH;Wang, MR
P63是新近发现的肿瘤抑制基因TP53的同源物，它编码多种具有反式激活、诱导死亡和显性负活性的同工型。P63表达于鳞状上皮和多种肿瘤的基底层细胞。为探讨p63在食管癌中的外显性，我们采用免疫组织化学和逆转录聚合酶链式反应(RT-PCR)相结合的方法，分析了p63在食管鳞癌、癌旁不典型增生和正常组织中的表达。结果表明，DeltaNp63mRNA在所有的恶性肿瘤组织和正常组织中均可检测到，而TAp63的表达极低或不表达。P63蛋白在51例肿瘤组织中有50例呈高表达，且在性别、年龄、分期、分级等方面无明显差异。11例异型增生中，10例异常细胞均呈p63强阳性表达。有趣的是，p63在96%(45/47)癌旁正常组织中表达，而在远离肿瘤的粘膜中仅47%(14/30)表达。大部分远离肿瘤的上皮细胞的染色强度弱于癌旁组织。在所有组织学正常的p63表达的上皮中，无论距离肿瘤有多远，免疫组织化学反应仅限于基底层和基底层。我们的数据表明，DeltaNp63是在食道上皮细胞和肿瘤中表达的主要亚型。P63的高表达可能是食管鳞癌的早期事件，可能在疾病的发生发展中起重要作用。(C)2002年Wiley-Liss，Inc.
p63 is a recently identified homologue of the tumor suppressor gene TP53, which encodes multiple isotypes with transactivating, death-inducing and dominant-negative activities. p63 is expressed in basal cells of squamous epithelia and many kinds of tumors. To explore the penetrance of p63 in esophageal cancer, we analyzed p63 expression in squamous cell carcinomas, adjacent dysplasia and histologically normal mucosa of the esophagus by combination of immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that the DeltaNp63 mRNA was easily detectable in all malignant and histologically normal tissues, whereas TAp63 presented extremely low or no expression. The p63 protein was highly expressed in 50 of 51 tumor tissues without significant difference in gender, age, stage and grade. Ten of 11 dysplasia exhibited strong p63 staining in all abnormal cells. Interestingly, p63 expression was observed in 96% (45/47) histologically normal epithelia adjacent to the cancerous tissues but only in 47% (14/30) mucosa far from tumors. Most of the epithelia far from tumors showed weaker staining than that adjacent to the cancerous tissues. In all the histologically normal epithelia with p63 expression, irrespective of the distance from the tumors, immunohistochemical reaction was restricted to the basal and suprabasal cell layers. Our data suggested that DeltaNp63 is the major isotype expressed in epithelia and tumors of the esophagus. Elevated expression of p63 is probably an early event in esophageal squamous cell carcinomas, which may play a significant role in the development of the disease. (C) 2002 Wiley-Liss, Inc.