Induction of the CBP transcriptional co-activator early during laryngeal carcinogenesis.
OBJECTIVE
CREB-binding protein (CBP) is a transcriptional "integrator" that is suspected of contributing to tumorigenesis. This is the first systematic morphologic study evaluating CBP expression in a large series of human laryngeal tissues containing normal epithelium, premalignant lesions (hyperplasia and/or dysplasia), and squamous cell carcinoma.


METHODS
Immunohistochemical methodology was performed on formalin-fixed paraffin-embedded sections by using a monoclonal anti-CBP antibody. CBP expression was screened and compared in 156 patients with various laryngeal histologic entities.


RESULTS
Nuclear expression of CBP was found in 44 out of 91 (48.4%) specimens with normal-appearing epithelium (46.2% weak and only 2.2% moderate positivity), 92 out of 100 (92%) with hyperplastic lesions (56% weak, 36% moderate/strong, and only 8% no positivity), 80 out of 103 (77.7%) with dysplastic lesions (45.6% weak, 32.1% moderate/strong, and 22.3% no positivity), 37 out of 45 (82.2%) with well-differentiated carcinoma (42.2% weak, 40% moderate/strong, and 17.8% no positivity), 31 out of 43 (72.1%) with moderately differentiated carcinoma (32.6% weak, 39.5% moderate/strong, and 27.9% no positivity) and eight out of 12 (66.7%) with poorly differentiated carcinoma (41.7% weak, 25% moderate/strong, and 33.3% no positivity). Statistical analysis and correlation of the intensity of nuclear immunostaining among the various histologic entities revealed statistically significant results.


CONCLUSIONS
Overexpression of CBP is detected from the very early stages of laryngeal carcinogenesis, suggesting that CBP may play a role in malignant transformation of precancerous laryngeal lesions. It is possible that overexpression of this protein is a prerequisite for the observed p53 upregulation in premalignant lesions, implying an indirect role of CBP in p53-mediated tumorigenic potential.
Karamouzis
M V
MV
Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece.
Papadas
T
T
Varakis
I
I
Sotiropoulou-Bonikou
G
G
Papavassiliou
A G
AG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050882:CREB-Binding Protein; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D002467:Cell Nucleus; D002471:Cell Transformation, Neoplastic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007818:Laryngeal Diseases / Q000235:genetics* / Q000473:pathology; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis*; D015534:Trans-Activators / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000494:pharmacology; D015854:Up-Regulation
D009687:Nuclear Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D050882:CREB-Binding Protein; C494363:CREBBP protein, human