The prognostic value of spontaneous apoptosis, Bax, Bcl-2, and p53 in oral squamous cell carcinoma of the tongue

Cancer. 1999 Sep 15;86(6):913-20. doi: 10.1002/(sici)1097-0142(19990915)86:6<913::aid-cncr4>;2-a.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis*
  • Biomarkers, Tumor / analysis
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins / analysis*
  • Proto-Oncogene Proteins c-bcl-2 / analysis*
  • Reproducibility of Results
  • Staining and Labeling
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / pathology*
  • Tumor Suppressor Protein p53 / analysis
  • bcl-2-Associated X Protein


  • BAX protein, human
  • Biomarkers, Tumor
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein