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. 1998 Sep;43(3):383–387. doi: 10.1136/gut.43.3.383

Loss of Bcl-2 expression correlates with tumour recurrence in colorectal cancer

M Ilyas 1, X Hao 1, K Wilkinson 1, I Tomlinson 1, A Abbasi 1, A Forbes 1, W Bodmer 1, I Talbot 1
PMCID: PMC1727241  PMID: 9863484

Abstract

Aims—To investigate the association between immunohistochemical expression of Bcl-2 and p53 in colorectal cancer and tumour recurrence following surgery. 
Methods—Sixty six cases of Dukes' B colorectal carcinoma were studied. All tumours were moderately differentiated and were shown to be histologically clear of the resection margins. Immunohistochemistry was performed on formalin fixed paraffin wax embedded tissue using monoclonal antibodies for p53 and Bcl-2. The Bcl-2 staining was assessed separately for relative intensity of staining and percentage of positive tumour cells and given a final score which combined the two factors. The p53 staining was assessed on number of positive tumour cells only. The patterns of immunostaining of those cases in which there had been tumour recurrence were compared with those cases in which there was no tumour recurrence (controls). 
Results—A statistically significant inverse association was found between Bcl-2 score and tumour recurrence (median Bcl-2 score of 6 (interquartile range (IQR) 2-9) in patients with recurrent disease; median Bcl-2 score of 8 (IQR 6-10) in those without recurrence; p=0.03). When examined separately, both the intensity of expression and percentage of positive tumour cells were significantly associated with tumour recurrence (p=0.04 in each case). There was no association between p53 staining and tumour recurrence. 
Conclusion—Results suggest that, when controlled for differentiation, Bcl-2 expression is a prognostic marker and may be useful as an adjunctive test in clinical decision making. 



Keywords: colorectal cancer; tumour recurrence; Bcl-2; p53; Jass grouping

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Figure 1 .

Figure 1

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Bcl-2 expression in non-neoplastic mucosa. There is intense Bcl-2 expression in the base of the crypts with a gradient of diminishing intensity along the crypt axis. The lymphocytes of the lamina propria are also positive and act as internal positive controls. 


Figure 2 .

Figure 2

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Heterogeneous expression of Bcl-2 in colorectal tumours. (A) Tumour which is negative for Bcl-2 expression while the peritumoural lymphocytes and adjacent mucosa can be seen to be positive. (B) Tumour showing weak but unequivocal expression in most tumour cells. (C) Tumour which is predominantly negative except for focal intense expression. (D) Intense expression can be seen in most tumour cells. 


Figure 3 .

Figure 3

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p53 expression in a colorectal tumour, showing strong nuclear expression in most tumour cells. 


Figure 4 .

Figure 4

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Scatter plots of Bcl-2 scores for (A) intensity, (B) percentage positive tumour cells, and (C) combined scores in the cancers of those patients in whom the tumours eventually recurred and those who remain free from recurrence. IQR, interquartile range. 


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