Expression of cyclin D1 and GSK-3beta and their predictive value of prognosis in squamous cell carcinomas of the tongue.
The status of cyclin D1 and glycogen synthase kinase 3beta (GSK-3beta) was investigated in 41 patients with T1 and T2 squamous cell carcinomas (SCCs) of the tongue. Out of the 41 SCCs, 27 (65.9%) showed overexpression of cyclin D1 in comparison with normal lingual epithelia by an immunohistochemical method. Cyclin D1 gene amplification was detected in only two (9.1%) of 22 informative cases of the SCCs by differential PCR. Expression of GSK-3beta, which was found to regulate proteosomal degradation of cyclin D1 protein, was reduced in 16 cases (39.0%) of the SCCs relative to normal epithelia, and the intensity of GSK-3beta staining showed an inverse association with cyclin D1. These findings suggest that overexpression of cyclin D1 primarily results from stabilization due to reduction of GSK-3beta, but not cyclin D1 gene amplification, in lingual SCCs. Kaplan-Meier analysis demonstrated that the patients with high cyclin D1 and reduced GSK-3beta expression had a significantly lower 5-year survival than the patients with low cyclin D1 and non-reduced GSK-3beta expression (P=0.014). The cyclin D1 and GSK-3beta coupled assessment was more valuable for the prediction of prognosis than assessment based on cyclin D1.
Goto
H
H
Department of Oral and Maxillo-Facial Surgery, Faculty of Medicine, Oita Medical University, 1 Idaigaoka, Hasama-machi, Oita, Japan.
Kawano
K
K
Kobayashi
I
I
Sakai
H
H
Yanagisawa
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3