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

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.

SUBMITTER: Ilyas M

PROVIDER: S-EPMC1727241 | biostudies-other | 1998 Sep

REPOSITORIES: biostudies-other

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Project description:BackgroundInhibitor of DNA binding/Inhibitor of differentiation 4 (ID4) is a critical factor for cell proliferation and differentiation in normal vertebrate development. ID4 has regulative functions for differentiation and growth of the developing brain. The role of ID1, ID2 and ID3 are expected to be oncogenic due to their overexpression in pancreatic cancer and colorectal adenocarcinomas, respectively. Aside from these findings, loss of ID3 expression was demonstrated in ovarian cancer. The aim of the present study was to reveal the factual role of ID4 in carcinogenesis in more detail, since its role for the pathogenesis of human breast cancer has been discussed controversially, assigning both oncogenic and tumour suppressive functions.MethodsID4 promoter methylation, ID4 mRNA expression and ID4 protein expression were analysed in primary human breast cancer specimens using methylation-specific PCR (MSP) (n=170), semiquantitative realtime RT-PCR (n=46) and immunhistochemistry (n=3), respectively. In order to demonstrate a functional association of ID4 promoter methylation with its gene silencing, we performed DNA demethylation analysis with four human breast cell lines using MSP and semiquantitative realtime RT-PCR. In addition, we performed correlations of ID4 promoter methylation with ID4 mRNA and ID4 protein expression in matched samples of breast tumour and corresponding normal tissue. We carried out statistical analyses in order to find correlations between ID4 promoter methylation and clinicopathological parameters.ResultsFrequent ID4 promoter methylation was observed in primary breast cancer samples (69%, 117/170). We found a tight correlation (P<0.0001) between ID4 promoter methylation and loss of ID4 expression in primary breast cancer 3 specimens. Demethylating treatment with breast cancer cell lines was associated with clear ID4 mRNA re-expression. Tumours with ID4 promoter methylation showed distinct loss of ID4 expression on both transcription and protein level. Interestingly, ID4 promoter methylation was a factor for unfavourable recurrence-free survival (P=0.036) and increased risk for lymph node metastasis (P=0.030).ConclusionID4 is indeed a novel tumour suppressor gene in normal human breast tissue and is epigenetically silenced during cancer development, indicating increased risk for tumour relapse. Thus, ID4 methylation status could serve as a prognostic biomarker in human breast cancer.

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

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