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The prognostic value of spontaneous apoptosis, Bax, Bcl‐2, and p53 in oral squamous cell carcinoma of the tongue
Author(s) -
Xie Xin,
Clausen Ole Petter F.,
Angelis Paula De,
Boysen Morten
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19990915)86:6<913::aid-cncr4>3.0.co;2-a
Subject(s) - tunel assay , apoptosis , immunostaining , immunohistochemistry , terminal deoxynucleotidyl transferase , bcl 2 associated x protein , bax protein , pathology , medicine , basal cell , cancer research , programmed cell death , andrology , biology , protein expression , gene , caspase 3 , biochemistry
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. Cancer 1999;86:913–20. © 1999 American Cancer Society.