Elevated expression of p63 protein in human esophageal squamous cell carcinomas.
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.
Hu
Hai
H
National Laboratory of Molecular Oncology and Department of Pathology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Xia
Shu-Hua
SH
Li
Ai-Dong
AD
Xu
Xin
X
Cai
Yan
Y
Han
Ya-Ling
YL
Wei
Fang
F
Chen
Bao-Sheng
BS
Huang
Xiao-Ping
XP
Han
Yu-Sheng
YS
Zhang
Jian-Wei
JW
Zhang
Xun
X
Wu
Min
M
Wang
Ming-Rong
MR
D002294:Carcinoma, Squamous Cell / Q000737:chemistry*; D004268:DNA-Binding Proteins; D004938:Esophageal Neoplasms / Q000737:chemistry*; D004947:Esophagus / Q000737:chemistry; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins; D010750:Phosphoproteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D025521:Tumor Suppressor Proteins
C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins