Abstract
bcl-2 is one of a family of genes that control the apoptotic threshold of a cell. bcl-2 protein and its anti-apoptotic homologue, mcl-1, with the pro-apoptotic protein, bax, are thought to function by forming homo- and heterotypic dimers that then control the progression to apoptosis. p53 is also involved as a down-regulator of bcl-2 and a promoter of bax. To determine the effect of these apoptotic mechanisms, we used immunohistochemistry to determine the prognostic significance of the expression of bcl-2, mcl-1, bax and p53 in primary and recurrent cervical cancer. Tissues from 46 patients with primary cervical cancer and 28 women with recurrent carcinoma were stained for bcl-2, mcl-1, bax and p53. Kaplan-Meier survival analysis was performed using the log-rank test for differences between groups. In the primary disease group, positive staining for bcl-2 was associated with a better 5-year survival (bcl-2 +ve, 84% vs bcl-2 -ve, 53%, P = 0.03). Positive staining for p53 was associated with a survival disadvantage (p53 +ve, 4-year survival 38% vs p53 -ve, 4-year survival 78%, P = 0.02). mcl-1 and bax staining were not useful as prognostic indicators in primary disease. No marker was prognostic in recurrent disease. Positive bcl-2 staining defines a group of patients with primary disease with a good prognosis. p53, an activator of the bax promoter, identifies a group with a worse outcome. In recurrent disease, none of the markers reflected prognosis.
Highlights
The process of carcinogenesis may be associated with increased stimulation of cell growth, loss of growth suppression, alterations in immune surveillance and changes in apoptosis
The objective of this study was to examine the prognostic significance of immunohistochemical detection of the bcl-2 family of apoptotic proteins and p53 in primary and recurrent cervical cancer
Details of the extent of staining for the antibodies are shown in Table 2. bcl-2 positivity (> 10% of the tumour) was recorded in 34% (15/44) of primary and 21% (6/29) of recurrent tumours. mcl1 positivity (> 70% of the tumour) was recorded in 57% (25/44) of primary and 75% (21/28) of recurrent cancers. bax staining (> 50% of the tumour) was seen in 37% (17/46) of primary and 48% (14/29) of recurrent cancers
Summary
The process of carcinogenesis may be associated with increased stimulation of cell growth, loss of growth suppression, alterations in immune surveillance and changes in apoptosis. P53 can induce apoptosis in some cells and can down-regulate bcl-2 (Miyashita et al, 1994). There appears to be an inverse relationship between p53 and bcl-2 expression in breast cancer (Haldar et al, 1994), ovarian cancer (Henriksen et al, 1995) and lymphoma (Nguyen et al, 1996). This suggests an interaction between these two factors in the regulation of programmed cell death. Several studies have examined the role of bcl-2 either alone (Tjalma et al, 1997) or in conjunction with bax (Uehara et al, 1995) in cervical cancer. The objective of this study was to examine the prognostic significance of immunohistochemical detection of the bcl-2 family of apoptotic proteins (bcl-2, mcl-I and bax) and p53 in primary and recurrent cervical cancer
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