The prognostic value of spontaneous apoptosis, Bax, Bcl-2, and p53 in oral squamous cell carcinoma of the tongue.
BACKGROUND
Bax, Bcl-2, and p53 proteins are involved in the regulation of apoptosis and have been reported to correlate with prognosis in several tumor types.


METHODS
Bax, Bcl-2, p53, and the level of spontaneous apoptosis were evaluated in formalin fixed, paraffin embedded pretreatment specimens from 85 T1-4 squamous cell carcinomas (SCCs) of the tongue by immunohistochemical methods. The percentage of apoptotic cells labeled by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP labeling (TUNEL) method was expressed as an apoptotic index (AI). For Bax and Bcl-2 evaluation, the fraction of tumor cells stained and the staining intensities were given scores that were added together, resulting in a final score. p53 immunostaining was expressed as a percentage of positive cells.


RESULTS
High AI was significantly associated with high Bax expression (P = 0.0122) and highly differentiated tumors (P = 0.0062). No correlation was found between AI and Bcl-2 expression. There was no correlation between p53 positivity and any of the other apoptosis-related parameters. Whereas low AI scores and low Bax expression correlated significantly with poor prognosis (P = 0.0053 and P = 0.0012, respectively), a low Bcl-2 expression was associated with a favorable clinical outcome (P = 0.0262). Patients with a high Bcl-2/Bax expression ratio had a significantly poorer prognosis than those with a low ratio (P < 0.0001). Multivariate analysis revealed that Bax expression, the Bcl-2/Bax expression ratio, and the T and N classifications were significantly independent prognostic variables. The Bcl-2/Bax expression ratio was the strongest independent prognostic parameter.


CONCLUSIONS
AI, individual Bax and Bcl-2 expression, and particularly the Bcl-2/Bax expression ratio have prognostic value in SCC of the tongue.
Xie
X
X
Department of Otolaryngology, The National Hospital, University of Oslo, Oslo, Norway.
Clausen
O P
OP
De Angelis
P
P
Boysen
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D015203:Reproducibility of Results; D013194:Staining and Labeling; D014062:Tongue Neoplasms / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein