The role of p63 and deltaNp63 (p40) protein expression and gene amplification in esophageal carcinogenesis.
p63, a member of the p53 gene family, is known to encode functionally antagonistic protein isoforms. Although transactivating protein isoforms display p53-like functions, deltaNp63 isoforms act toward p53 in a dominant negative way. Using immunohistochemistry, we examined the expression of pan-p63 and deltaNp63 in 50 esophageal squamous cell carcinomas (SCCs) as well as in squamous low-grade intraepithelial neoplasias (S-LGINs; n = 4) and high-grade intraepithelial neoplasias (S-HGINs; n = 18). Additionally, 50 esophageal adenocarcinomas (ADCs) that arose in Barrett's esophagus (BE) as well as adjacent specialized metaplastic epithelium (SE; n = 41), low-grade intraepithelial neoplasias (B-LGINs; n = 27), and high-grade intraepithelial neoplasias (B-HGINs; n = 21) in BE were investigated. Furthermore, p63 gene amplification was determined by fluorescent differential polymerase chain reaction in a subset of 10 SCCs and 10 ADCs. Whereas in normal esophageal epithelium, expression of pan-p63 is invariably restricted to the basal cell layer, in 100% of S-LGINs, 94.4% of S-HGINs, and 88.0% of SCCs, expression of p63 was found in >75% of the cells. Concerning BE, only in a small subset of SEs (7.3%), B-LGINs (14.8%), B-HGINs (14.3%) and ADCs (16.0%) was a weak p63 protein expression (<10% positive cells) detectable, whereas the rest of the samples were completely negative. Expression of deltaNp63 was identical to expression of pan-p63 in the vast majority of samples. p63 gene amplification was found in 2 of 10 (20.0%) investigated SCCs and in 1 of 10 (10.0%) ADCs. In summary, strong expression of p63, especially its deltaNp63 isoforms, is a frequent finding in esophageal precancerous and cancerous squamous lesions, whereas this is not the case in carcinogenesis of BE. p63 gene amplification is an infrequent finding in esophageal SCCs and ADCs and does not correlate with protein overexpression.
Geddert
Helene
H
Institute of Pathology, Department of Surgery, University of Düsseldorf, Germany.
Kiel
Sibylle
S
Heep
Hans Jörg
HJ
Gabbert
Helmut Erich
HE
Sarbia
Mario
M
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
C081876:CKAP4 protein, human; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins